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AETIOLOGY DEFINITION AND CLASSIFICATION

Definition

Aetiology is defined as study of causation of disease.

Classification There are several agents or factors that can produce disease in animals and which originate from within the body or outside the body. Thus, the causes are broadly classified into two categories.
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Predisposing causes (Intrinsic factors) Definitive causes (Extrinsic factors) o Predisposing causes make the animal susceptible to definitive causes. These include o Heredity-Inherited-Glycogen storage diseases e.g. Pompe‘s disease (Lysosmal acid maltase deficiency) in cattle, dog o Species-Rinderpest is found in cattle not in other animals. o Breed-Certain breeds are more susceptible to some diseases than others. Heavier breeds of dogs suffer from bone diseases o Age-Young animals are comparatively more prone for disease than adults. o Sex-Diseases of reproductive organs in respective sex.

Colour (Pigmentation)-Sunburns in melanin deficiency, eye cancer in Hereford cattle

DEFINITIVE CAUSES
Definitive causes are actual agents that produce diseases. These are Physical causes
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Trauma-Mechanical, Accidents Excess heat-Burns Excess cold-Frost bite, cold shock Radiation-UV irradiation, x-radiation

Chemical causes
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Acids-HCl, H 2 SO 4 Alkalis-NaOH Inorganic chemicals-HgCl 2 is nephrotoxic Organic chemicals-CCl 4 -Hepatotoxic

Viable/biological causes
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Bacteria-Anthrax bacilli Viruses-Foot and mouth disease virus (Picorna virus) Mycoplasma-Respiratory disease in chicken Rickettsia-Ehrlichiosis Fungus-Dermatomycosis, aspergillosis (e.g. Brooder pneumonia in chicks) Parasites-Haemonchosis in ruminants, ascaridiasis (Pups, buffalo calves)

Nutritional causes
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Excess-Hypervitaminosis A, D Deficiency-Hypoproteinaemia, hypovitamonosis (e.g. Xerophthalmia in vitamin A deficiency, star gazing in chicken in vitamin B 1 deficiency), Hypocalcaemia (Milk fever in high yielding cows)

Immunological diseases-Hypersensitivities-Anaphylaxis Toxins-Phytotoxins, Zootoxins (Snake venom), Pesticides (Organochlorines, organophosphorus compounds) Physical causes-Traumatic injuries
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Perforation is a wound caused by a bullet or nail. Laceration is a wound in which there is tearing of tissues. e.g: Automobile accidents. Concussion is a violent shock caused by an injury and is usually applied to injuries of the head. There may or may not be loss of consciousness. Sprain is an injury of joint in which there may be stretching or rupture of ligaments, muscles or tendons. In this anatomical relationship of the structures is maintained. Luxation or dislocation is deviation from its original position in which the anatomical relationship are not maintained and the ligaments may be torn. Fracture is discontinuity of a bone.

Miscellaneous causes
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Atrogenic disease is a condition produced by the physician by over or needless medication. Idiosyncrasy is different reaction of animals to drugs.

DISTURBANCES IN DEVEOPMENT (ANOMALIES & MONSTER)
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Anomaly is developmental defect affecting an organ or part of the body. Anomaly is the disturbance of development that involves an organ or a portion of an organ. Monster is an animal in which extensive abnormal developments are present. A Congenital disease is one in which the patient is born with the disease whereas an inherited disease is one which is due to factors in the genetic materials received from the parents.

CLASSIFICATION OF ANOMALIES
A. Arrest of Development 1. Agenesia is an incomplete and imperfect development of an organ or part and aplasia is absence of an organ or part.
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Acrania is absence of most or all of the bones of the cranium. Amelia is absence of one or more limbs. Anencephalia is absence of the brain. Hypocephalia is incomplete development of the brain. Hemicrania is absence of half of the head.

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Exencephalia is defective skull with brain exposed or extruded. If the protruding brain contains a ventricle which is filled with excessive amount of fluid, the malformation is a hydrencephalocele. Arhinencephalia is absence or rudimentary development of the olfactory lobe with corresponding lack of development of the external olfactory organs. Agnathia is absence of the lower jaw. Anophthalmia is absence of one or both eyes. Abrachia is absence of the forelimbs. Abrachiocephalia is absence of forelimbs and head. Adactylia is absence of digits.

2. Fissures on the median line of the head, thorax, and abdomen.
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Craniooschisis (skull) Cheiloschisis (lip), often referred to as harelip. Palatoschisis (oral) cavity, often called cleft palate. Harelip and cleft palate result from faulty development of the maxillary process derived from the first visceral arch. Rachischisis (spinal column). Schistorrachis or spina bifida (spinal column) Schistothorax (thoraz or sternum). Schistosomus (abdomen). Schistocormus (thorax, neck or abdominal wall). Results from arrested development of the amnion.

3. Fusion of paired organs
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Cyclopia (eyes) Ren arcuatus (kidneys), often referred to as horseshoe kidney.

B. Excess of Development 1. Congenital hypertrophy

Hemi hypertrophy (partial)

2. Increase in the number of a part
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Polyotia (ears) Polyodontia(teeth) Polymelia (limbs) Polydactylia(digits) Polymastia (mammary gland) Polythelia(teats)

DISPLACEMENTS DURING DEVEOPMENT
A. Displacements of organs
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Dextrocardia is transposition of the heart to the right side. Ectopia cordis cervicalis is displacement of the heart into the neck.

TWINS UNITED A. Freemartin is a female calf having arrested development of the sex organs and being the twin of perfect male.     Pygopagus – united in the pelvic region with the bodies side by side. limbs and other recognizable features (amorphous). They develop from a single ovum. or teeth depending on the species and often arranged as an epidermal cyst (Dermoid cyst).    Craniopagus – brains usually separated. For the most part monsters possess a duplication of all or most of the organs and other parts of the body. doubling may also affect the neck. Odontoid cyst is inclusion within an individual of a mass of dental enamel and cement. Displacements of tissues        Teratoma is inclusion of multiple displaced and also neoplastic tissue within an individual. thorax and trunk. Such monsters may lack a head (acephalus). Dermoid is inclusion within an individual of a mass containing skin. feathers. Dicephalus – two separate heads. . hair. B. Classification of the Monsters   Twins Entirely Separate o Although separate. Ischiopagus – united in the pelvic region with the bodies at an obtuse (not pointed) angle. these twins are in a single chorion. but having also either a unisexual or bisexual development of the other parts of the genitalia. Posterior Twinning: The posterior part is double. bodies as a rule at an acute angle. only the face doubled. They are therefore the product of incomplete twinning. the anterior single. MONSTERS A monster or monstrosity is a disturbance of development that involves several organs and causes great distortion of the individual. Anterior Twinning: The anterior part of the individual is double. lungs. Cephalothoracopagus – union of head and thorax. Diproosopus – doubling in the cephalic region without complete separation of heads. the other is malformed (acardius). Dentigerous cyst is inclusion within an individual of one or more imperfectly formed teeth. the posterior single. Fusion of Sexual Characters Hermaphrodite is an individual having both testicular and ovarian tissue. One twin as a rule is well developed. Dipygus – doubling of posterior extremities and posterior part of body. In the malformed foetus there is arrested development of the heart. or the trunk (acormus). Twins United o These twins are more or less completely united and are of symmetrical development.B. and trunk. Pseudohermaphrodite is an animal having unisexual development of the sex glands (either testicular or ovarian tissue).

Prosopothoracopagus – besides the union the thorax the abdomen.C. The pair is joined in the region of the thorax.    Thoracopagus – united only by the thorax. and also often in the abdominal region. HAEMODYNAMIC DERANGEMENTS-1 HYPERAEMIA AND CONGESTION Definition  Hyperaemia is increased volume of blood in affected tissue or part. Hyperaemia (Active hyperaemia)   Occurs in arterioles or arteries Increased blood flow in capillaries Congestion (Passive hyperaemia)   Occurs due to impaired venous drainage Stasis of blood in veins CLASSIFICATION OF HYPERAEMIA . ventral arrangement of the foetuses. Twinning Almost Complete: Duplication of the whole trunk or the anterior or posterior extremities with parallel. the head and neck are united. Rachipagus – thorax and lumbar portion of the spinal column united.

ACUTE GENERAL ACTIVE HYPERAEMIA Increased blood throughout the body Causes   Various systemic diseases. heary ↑ warmth in Skin . swollen.g.due to retention of fluids Macroscopically  Bright red color or organs Microscopically  Arteries and capillaries dilated with blood Result  Disappears if cause is removed ACUTE LOCAL ACTIVE HYPERAEMIA   Increased amount of blood in arterial system within a local area (leg. lung) Most common type of hyperaemia Causes  Physiological o Occurs in stomach and intestine following a meal o Lactating mammary gland o Muscles during exercise o Genital tract during oestrus Blushing  Acute inflammation Macroscopically   Enlarged. erysipelas o Rapidly beating heart → increased blood supply Renal diseases .increase metabolism It is beneficial. Pasteurellosis. Stomach. E.ACTIVE HYPERAEMIA       Increased blood in arterial side Usually due to inflammation All active hyperaemia are acute Chronic active hyperaemia does not occur Occurs when there is a demand for oxygen and nutrients .

Microscopically   In live animals. Haemothorax. Macroscopically  Organs are blue in color (Unoxygenated blood) .) lungs.if vein of an organ or body It can be acute or chronic Brain congestion  Chonic venous congestion is more common ACUTE GENERAL PASSIVE HYPERAEMIA   Increase in the amount of blood on the venous side of circulatory system Due to sudden obstruction to the flow of blood in heart and lungs. etc. GRNERAL . etc. Haemopericadium. Causes      Heart failure o Degeneration and necrosis of myocardium o Myocardial infarction Pneumonia Pulmonary thrombosis or embolism Hydropericardium. Hydrothorax. arteries. heart LOCAL .e. arterioles and capillaries are distended with blood Difficult to detect in dead animals PASSIVE HYPERAEMIA OR CONGESTION     Increased blood in the venous end due to improper drainage.if interference is central (i.

atrophy). Causes due to central lesions in heart and lungs    Heart lesions o Stenosis of valvular openings Valvular insufficiency o Failure of cusps of valves to close property o Inflammatory tissue o Thrombus Myocardial failure o Degeneration and necrosis of muscles o Degeneration and necrosis of muscles Contraction of muscles ↓ Blood pushed in arteries ↓ But accumulates in venous side  Anomalies of heart o Persistent foramen orale o Interventricular septal defects Blood moves from one chamber to another ↓ Arterial blood pressure maintained ↓ Blood accumulates in venous end. . heavy Upon incision. blood oozes out Result   Causes are mild → Recovery Causes are severe → Death CHRONIC GENERAL PASSIVE HYPERAEMIA Increased blood on venous end persisting for long period of time causes Permanent changes (fibrosis.   Veins distended with blood Organs enlarged.

  Constrictive lesons in pericardium o Traumatic pericarditis in cattle Lesions of lungs o Obliteration of capillary bed in lungs o Prevents free flow of blood through the lungs o Retards flow through right side of heart o Blood back flows into Liver o Causes  Chronic alveolar pulmonary emphysema in horses (BROKEN WIND)  Pneumonia  Hydrothorax. ―Nutmeg pattern‖ Liver . haemothorax o Compression of major pulmonary vessels  Tumours  Cysts  Abscesses Lesions in CVC Liver    Lesions in Rt A-V valve or lungs Increase in size and weight on section.CVC    Central veins are prominent Area surrounding central vein is congested Congested area is surrounded by hypoxic areas Morphologic features of CVC   Veins all over the body engorged with blood Blood is bluish red in color .

   Oedema of tissues Atrophy of organs Degeneration and Necrosis or organs Microscopically Mitral valve diseases ↓ Affected in Left – sided heart failure ↓ Alveolar capillaries distended with blood ↓ Rupture of capillaries ↓ Minute intra – alveolar haemorrhages ↓ Haemosiderin release from RBCs ↓ Phagocytosed by macrophages ↓ Heart failure cells (Macrophages) ↓ Fibrosis (induration) of alveolar septa ↓ Brown induration of lungs ↓ (due to haemosiderin) .

bandages Pathogenesis . enlarged and dark purple Cortico-medullary junction – dark red in color ACUTE LOCAL PASSIVE HYPERAEMIA Increase in blood in the veins of a portion (foot. tourniquets. kidney etc) Due to sudden obstruction to blood flow Causes   Malposition of viscera o Volvulus. intussusception. tail. torsion External pressure o Ligatures.Spleen      Enlarged and cyanotic Due to congestion of Liver Occurs in vegetative endocarditis (swine) and Traumatic pericarditis (cattle) Hard and indurated .Cyanotic induration Kidneys    Pressure on renal veins by o Tumours of adrenals o Abscesses Grossly.

increase capillary bed Intestine & kidneys – necrosis and gangrene Causes pneumonia and gangrene of intestine Significance  Indicates o the side of animals which was ventral at the time of death o Heart was not able to pump properly o Location of body in medico–legal cases Grossly and microscopically .HYPOSTATIC CONGESTION Accumulation of blood in ventral portions of the body due to gravity.Agonal congestion Appearances     Veins in ventral portion or organs distended with blood Lungs . Causes      Occurs in heart diseases Recumbency Inactive animals Large animals Heart failure .

Veins are engorged with blood ↓ Necrosis of endothelial cells ↓ Haemorrhage CHRONIC LOCAL PASSIVE HYPERAEMIA   Increase in amount of blood for a long time in veins Permanent tissue changes (atrophy. Two types   Haemorrhage by rhexis : When there is rupture of a blood vessel Haemorrhage by diapedesis : When blood leaves through intact blood vessels . abscesses Obstruction from within o Thrombus (blood clot) Gross and microscopic appearance     Enlarged initially later undergoes atrophy Veins .bluish blood Oedema due to increase permeability of capillaries Fibrosis HAEMORRHAGE Definition  It is the escape of blood from a vessel. fibrosis) Causes   External pressure o Tumors.

Spleen .Site of haemorrhage Epistaxis Bleeding from nose Haematemesis Blood in vomit Haemoptysis Metrorrhagia Enterrohagia Melena Haematuria Haemothorax Haematocoel Blood in sputum Bleeding from uterus Bleeding from intestine Blood in stools Blood in urine Blood in thoracic cavity Bleeding into tunica vaginalis Apoplexy Hemosalphinx Bleeding in oviducts Hematoma Apoplexy Tumour-like accumulation of blood Haemorrhage into brain Size of haemorrhage     Petechiae: minute.Spleen Ecchymoses . pinpoint Purpura: approximately 1cm in size Ecchymoses: 1 – 2 cm in size Extravasation: Larger area Petechiae-Intestine Purpura .

incisions.Seen in race horses Hypoxia and lack of nutrition o Passive venous congestion → damage to endothelium . haemorrhagic septicaemia. Delayed clotting Thrombocytopenic purpura: Decrease in platelets seen in toxaemias Nutition o Deficiency of vitamin K .Extravasation Source of haemorrhage     Internal haemorrhages-Abdominal cavity Cardiac Arterial Venous Capillary Causes   Conditions affecting the blood vessels Conditions affecting the blood Conditions affecting blood vessels        Trauma: Lacerations. swine erysipelas.ASPHYXIA Increased blood pressure o Excessive exercise → increased blood pressure → Rupture of blood vessel . haemorrhagic septicaemia Necrosis of vessel wall o Ulcers in gastric mucosa o Neoplasms Diseass of vessel walls o Aneurysm . anthrax.Haemorrhage Conditions affecting blood constituents    Haemophillia: Hereditary sex linked disease. chloroform. contusions Clumps of bacteria.g.e. black quarter o Viral : Hog cholera o Chemicals : Arsenic. Strongylus vulgaris infection in horses o Atheroma Toxic injury to capillary endothelium o Bacterial : Anthrax. cyanide o Enterotoxins : Sheep & calves – Clostridium welchii . phosphorus.

e. iron is recaptured and haemoglobin is synthesized. Haemorrhage in pericardial sac (CARDIAC TAMPONADE) is fatal.  Vitamin K which is required for prothrombin formation and in its absence clotting will not take place. Invitamin C defeciency capillary endothelium becomes more fragile leading to haemorrhage Heparinoid state o In anaphylactic shock and irradiation. excess of heparin is found which impairs clotting.g. Stomach worm infection Site of haemorrhage is very important. site. Sudden loss of about 30% of blood volume or slow losses of large volume of blood will have no clinical significance. WBCs move into blood vessels and RBCs are phagocytosed . Iron deiciency anaemia is due to repeated and chronic loss of blood from external surface When erythrocytes are retained in body cavities.  Increased use of sulpha drugs may not permit intestinal microflara to synthesis vitamin K o Deficiency of vitamin C  Vitamin C is required for formation of ground substance. Small haemorrhage in brain is fatal whereas small haemorrhage in skeletal muscle or subcutaneous tissue is NOT FATAL. Fate of haemorrhage  In small haemorrhage fluid portion is reabsorbed. tissues. Plant toxins o Brakern fern and sweet clover poisoning prevent prothrombin formation  Microscopical appearance   Presence of erythrocytes outside blood vessels Recent haemorrhage stains deeply Haemorrhage disintegrates due to action of tissue enzymes ↓ Haemoglobin  Haemosiderin (Iron) and hamatoidin (Non iron) ↓ Bilirubin ↓ Phagocytosed by macrophages  Prussian blue reaction reaction to demonstrate iron Significance and result     Depends on volume. joints. rate.

 In larg haemorrhage. Inflammatory oedema 2. RBCs are haemolysed and haemoglobin is split into haeme (Haemosiderin which is iron containing portion of haeme and haematoidin is iron free portion) and globin. Arrest of haemorrhage Vascular contraction Platelet aggregation Clot formation Tissue pressure Small blood vessels White clot Red clot → When blood flow is slow   Increased perivasular pressure in tissue Decreased intra vascular pressure Decreased blood pressure Large harmorrhage ↓ Decreased BP ↓ No bleeding OEDEMA Definition  Abnormal accumulation of fluid in the intercellular tissue spaces or body cavities o Localized : Due to obstruction of venous outflow – leg o Generalized : Chronic venous Congestion or heart failure Terms used to describe oedema     Anasarca: Generalized subcutaneous oedema Ascites: Fluid in peritoneal cavity Hydrothorax. Non-inflammatory odema Mechanism of oedema formation Two forces called ―STARLING‘S FORCES ―   Filtration force: Expels fluid from the vessel Absorption force: Draws fluid into the vessel Physiology of fluid balance . Edematous fluid in thorax Hydropericardium: Edematous fluid in pericardium Oedema is of two types 1.

  At the arterial end of capillary hydrostatic pressure is 45mm of Hg and osmotic pressure of blood is 30mm of Hg (due to albumin / globulin). absorption force is 15mm of Hg CAUSES OF OEDEMA      Decreased plasma osmotic pressure Increased hydrostatic pressure Increased permeability of vascular endothelium Lymphatic obstruction Sodium retention Decreased plasma osmotic pressure .  This type of oedema is mild. At te venous end. whereas osmotic pressure is 30mm Hg. the rate of fluid flow in to vein is 5mm Hg. fluid expelled into the intercellular space (filtration force) is 15mm Hg.More fluid flows into intercellular space Hydrostatic pressure at arterial end is 45mm Hg and osmotic pressure at arterial end is 20mm Hg. hydrostatic pressure of blood falls to 15mm of Hg and osmotic pressure of blood is 30mm of Hg.Renal odema Increased hydrostatic pressure   General or passive hyperaemia → venous stasis Central lesion in heart or lungs or local obstruction in a vein Hydrostatic pressure at arterial end is 45mm Hg. Therefore. Increased permeability of capillary endothelium   Due to venous stasis → increased hydrostatic pressure Inflammation . So the rate of fluid accumulating in tissues is 5mm Hg. At the venous end. the rate of fluid accumulation in tissues is 20mm Hg Decreased plasma osmotic pressure mostly results in generalised and severe oedema     Malnutrition In advanced hepatic disease (Cirrhosis).stomach worms → Parasitic oedema Kidney or renal amyloidosis – blood lost in urine . protein synthesis will be affected leading to nutritional or cachetic oedema Loss of protein through intestine and stomach . Therefore. The rate of fluid flow into vein is 10mm Hg. Osmotic pressure at venous end is 20mm Hg and hydrostatic pressure is 15mm Hg. the rate of fluid flow into tissues is 25mm Hg. Thereby. Mainly the cause is in the heart.Low osmotic pressure in the blood . Because of the pressure diffeences ( Hydrostatic and osmotic pressure) at the arterial and venous end.Hypoproteinemia (Albuminemia)   Decreased protein synthesis Excessive loss from blood . Hence called cardiac oedema. osmotic pressure is 30mm Hg and hydrostatic pressure is 25mm Hg. So. So the rate of fluid flow into tissues is 15mm Hg.

water will be retained leading to generalized oedema Differences between transudate and exudate S. creamy. No. cyst. < 3% Low Low None None Exudate Cloudy. WBCs High Present Present Macroscopical appearance     Swollen. bandages. increase in weight Cold due to decrease blood.015 or less Low.humans Inflammatory conditions – farcy. thrombi Parasites (Demodex canis. RBCs.018 or higher High > 4% High. water like pale yellow Thin.Lymphatic obstruction Causes     Tumours. mites) Filariasis – Wucheria bancrofti . ulcerative lymphangitis In lymphatic obstruction. contains tissue fragments Have odour Acidic 1. watery no tissue fragments None Alkaline 1. white. yellow-red Thick. 1 2 3 4 5 6 7 8 9 10 Characters Colour Consistency Odour Ph Specific gravity Protein Cell count Enzyme count Bacteria Inflammation Transudate Clear. abscess. fluid and protein in intercellular space will not be drained leading to oedema (LYMPHOEDEMA) Sodium retention Causes    Congestive heart failure Nephrosis/Nephritis Acute renal failure Due to failure of excretion sodium in urine. flow and increase heat dissipation Less color No pain .

Increased permeability of endothelium .―INFLAMMATORY EXUDATE‖ 2.Fluid rich in protein pass out . Inflammatory oedema 2. Cardiac oedema 3. Cardiac oedema  Congestive heart failure leads to CVC which results in insufficient renal circulation ischaemia leading to oliguria with diminished chloride excetion.stains faintly pink .chronic cases Significance and result    Disappears if cause is removed Oedema in lung & brain are fatal Subcutaneous oedema impairs wound healing TYPES OF OEDEMA 1.   Incision results in flow of fluid from cut surface Pits on pressure Fibrosis Microscopical appearance      Space between adjacent cells widened During life space filled with fluid H&E stain . Myxoedema 8. Pulmonary oedema 6. Hunger/Famine/War oedema 5. Renal oedema 4. Inflammtory oedma  Toxins damage blood vessels . Cachetic oedema 7.fine granular material . Brisket disease 1.↑ pink if ↑ protein Atrophy of parenchymatous cells Fibrosis . Parasitic oedema 9. Angioneurotic oedema 10. This results in sodium retention which raises tissue osmotic pressure aggrevating oedema .

pericarditis Renal lesions Pressure on pulmonary veins by neoplasm Injury to brain Rapid removal of effusion from pleural / peritoneal cavity Poisons Infections . Pulmonary oedema  Causes o o o o o o o Cardiac failure .Oedema . 4. Chronic glomerulonephrtis o Hypertension for long period throws great strain on heart resulting in heart failure and thereby causing CVC which increases blood pressure in capillaries. As a resut of this. oliguria / Anuria results in sodium retention  Increased capillary permeability  Increased hydrostatic pressure in capillaries in venous side  Toxins damage kidney and heart causing cardiac failure and its outcome is CVC Subacue nephritis and nephrosis o Decreased colloidal osmotic pressure of blood o Increased sodium retention o Hypoalbuminaemia stimulates adrenal cortex to secrete increased amount of aldosterone which helps in reabsorption of sodium chloride. oedema in face and eyelids are usually seen.Abdominal cavity . This retained salt increases osmotic pressure and cause oedema.Ascites   Causes for cardiac oedema o Increased hydrostatic pressure of blood o Increased vascular permeability o Sodium retention Symptoms o Oedema of dependant parts o Traumatic pericarditis in bovines Cardiac oedema may develop in horses with chronic vesicular emphysema. 3. o Causes of acute glomerulonephritis are  Decreased osmotic pressure of blood  Toxins damage glomerular capillaries resulting in albuminuria and hypoproteinaemia. oedema occurs. Renal oedema    In acute glomerulonephritis (in man). valvular disease .  Increased osmotic pressure of ECF  In acute nephritis.hypertension. Hunger / Famine / war oedema   Hypoproteinaemia → Decreased plasma osmotic pressure War / famine → Decreased protein availability 5.

Brisket disease    Cattle moved to high altitude 9000ft above sea level develop oedema in abdomen. neck and jowl. protein. glottis. Adult flukes inhabitats bileduct causing chronic irritation of lining mucosa of the duct resulting in cirrhosis. haemorrhage & necrosis occurs in liver. Parasitic oedema   This type of oedema is most commonly seen in animals suffering with stomach worms.6. liver flukes. endogenous / exogenous allergens (plant. Angioneurotic oedema   In man. In this condition there will be increased protein accumulation in tissue fluid which raises pressure of fluid locally and water is drawn into the site. Reason for development of oedema in high altitude o Hypoxia o Chronic venous congestion . horses). 9. there will be an accumulation of fluid in lower jaw called as ―BOTTLE JAW‖ which is a characteristic feature of parasitic oedema. brisket. Cachetic oedema     Anaemia Wasting diseases Malnutrition Cardiac illness 7. 8. amphistomes. Myxoedma  This occurs in chronic thyroid deficiency. Affected liver cannot synthesis protein leading to oedema formation. fish meal) cause release of histamine which damage blood vessels and oedema results. Due to hypoproteinemia. allergens like snake venom produces hypersensitivity reaction which increases capillary permeability resulting in oedema in lips. Cardiac muscle becomes degenerated as it works in hypoxic condition and hence hypertrophied heart slowly dilates and which draws valves downwards resulting in valvuar incompetency and gives rise to chronic venous congestion.Develops due to increased capillary blood pressure and hypoxia . partial pressure of oxygen is decreased. thorax In animals (cattle. At high altitudes. 10. During migratory life of cercaria. The resulting hypoxia develops polycythemia (Increased viscosity of blood) and polypnoea (Increased heart beat).

erysipelothrix (vegetations) o Degenerations : Atherosclerosis (damage to intima) o Viruses : Hog cholera virus o Parasites : Strongylus vulgaris in anterior mesenteric artery in horses o Tumours : Invading tumours Mechanism of thrombus formation   Active o Antithrombotic factors and prothrombotic factors are seen on surface of endothelium Passive o Endothelium is thromboresistant wheras subendothelial connective tissue is highly thrombogenic. Antithrombotic factors (present on endothelial cells) .Inhibit thrombosis   Anticoagulant properties o Thrombo modulin .Protect against action of heparin and thrombin which converts fibrinogen to fibrin Anti platelet properties . i/r injection o Toxins : Streptococci.THROMBOSIS   Formation of clotted mass of blood within the cardiovascular system Clotted mass – Thrombus (singular) and thrombi (plural) Differences between thrombus and blood clot Thrombus Blood clot Formation Blood vessels Platelets Blood clotting system Composition Platelets Fibrin Prognosis Life threatening Causes for  Blood clotting system Only fibrin Life saving Injury to endothelium o Trauma : lacerations. laminin glycosoaminoglycans and thrombosporin. fibrinonectin. o Subendothelial onnective tissue consists of collagen. elastic. contusion.Inhibit platelet aggregation o Prostacyclin (PGI2) . rupture. o Damage to endothelium exposes the subendothelial connective tissue and activates intrinsic blood clotting pathway and platelet adhesion.

Increase blood lipids .Promotes fibrinolytic activity in blood and reacts against blood clots Thrombotic factors     Tissue factor (Thromboplastin) o Present on endothelium in small amounts o Activate extrinsic clotting pathway o Stimulated by  Endotoxins  Cytokines (IL – 1)  Tumour necrosis factor (TNF) von Willebrand factor (vWF) o Protein helps in platelet adherence thrombus Platelet Activating Factor (PAF) o Helps in platelet aggregation thrombus Inhibitor of Plasminogen Activator o Prevents fibrinolysis thrombus Normal homeostasis: There will be a balance between antithrombotic and prothrombotic factors in normal endothelium.Increase platelet aggregation .Coronary thrombosis Alterations in normal blood flow   Slowing of blood flow results in platelet aggregation Turbulence damage endothelium . Thrombus formation   Increase prothrombotic factors Decrease antithrombotic factors Alterations in constituents of blood         Increase in number of platelets o Parturition o surgery Increase in adhesiveness of platelets o Parturition o Surgery Decrease in heparin (anticoagulant) in diseases Increased plasma fibrinogen and prothrombin o Trauma Increased viscosity of blood o Dehydration o Polycythemia Sludging of blood o Clumping of cells Increased fragility of RBCs Increased cortisone therapy – Rheumatoid arthritis . o Nitric oxide (NO2) Fibrinolytic properties o Tissue plasminogen activator (tPAs) .

black quarter o Caused by Clostridium chauvoei Valvular thrombus o Pigs – Streptococcus pyogenes. Venous thrombi     Phlebothrombosis Common in bed ridden patients Rare in animals Seen in recumbent calves . bed ridden patients CLASSIFICATION OF THROMBI I. If it is large. Erysipelothrix rhusiopathiae o Cattle– Cornybacterium pyogenes o Horses– Streptococcus equi Ball thrombus: Seen in auricle .Unattached.horses Humans o Leg veins – Congestive heart failure.Types of thrombus    Arterial thrombus Venous thrombus Cardiac thrombus Causes for slowing of blood    Chronic venous congestion venous stasis Old and debilitated animals Varicose veins Comon sites for thrombosis   Animals o Scrotal plexus .Cardiac thrombi    Mural thrombus: Seen on the wall of left auricle o Bovines . Based on location within blood vascular system 1. Arterial thrombi   Located within arteries Common in domestic animals o Horses : Strongylus vulgaris larvae in anterior mesenteric artery o Dogs : Spirocerca lupi in aorta o Cattle: Onchocerca armillata in aorta 3.it causes valvular obstruction 2.horses o Vascular sinuses – horse and cows (Nasal passage) o Large veins of Broad ligament of uterus – cow o Anterior mesenteric artery .

Strongylus vulgaris (Horses) and Dirofilaria immitis (Dogs) IV.increase blood flow to legs – White Thrombus  Rest .Bacteria Aseptic thrombi . RBCs and WBCs and are seen in veins ( Commonly seen) Mixed Thrombi –Mixture of White and red thrombi (White . iliac veins Animals Nasal vascular sinuses – Cow.Leg veins collapse and press against hard surface. horses Veins of broad ligament – Cow o Scrotal plexus – Horses 4.Femoral.Formed during fast flow of blood. Classification based on colour of thrombi     Pale / White Thrombi .composed of platelets and are seen in heart / aorta Red Thrombi – composed of platelets / fibrin.Red Thrombus Fate of thrombus  Propagation : Enlargement . In general passive hyperaemia. veins will be distended and leads to slowing of blood which favours thrombus formation. Classification based on infectious agent    Septic thrombi .Attached to entire circumference of vessel Saddle thrombi -Site of bifurcation of blood vessel Canalised thrombi . Endothelium gets damaged and thromboplastin is released resulting in thrombus formation. Capillary thrombi   Seen in inflammation Injury to endothelium 5. popliteal.New blood channel is formed through clot III. Lymphatic thrombi   Seen in lymphatics draining inflammation area Beneficial II.Valves Lateral thrombi .Formed during sluggish flow) Laminated thrombi o Type of mixed thrombi  Excessive exercise .increase blood flow to legs .obstruction of vessel . Classification based on location within heart or bood vessels       Mural thrombi .Without bacteria / parasites Parasitic thrombi .Attached to one side of blood vessel Occlusive thrombi . Red . Locations     Human .Attached to wall of heart / blood vessel Valuvlar thrombi .

Control of haemorrhages Harmful effects . carotid arteries Beneficial effects .     Contraction : Shrinkage of thrombus may occur due to contraction of fibrin Embolus : Carried to other sites. mixed Yes Damaged Platelets Postmortem clot Small Smooth / glistening Red / yellow No Undamaged Fibrin Rapidity of blood flow Formed in flowing stream Stagnant stream Animal Organization Structure Living Yes Dead No Laminated (Line of Zahn) Homogenous .Vessel without collateral circulation o Infarction o Embolism o Passive hyperemia o Lymphoedema o Aneurysm – Strongylus vulgaris o Gangrene – intestinal thrombus o Colic.Jugular vein. and cause dangerous infarction o Enzymes from WBCs / platelets digest thrombi and emboli are formed Abscessation : Pyogenic bacteria in thrombus may gives rise to bacterial emboli Resolution : Fibrinolysis o Fresh thrombus – Complete digestion o Old thrombus – incomplete digestion Organization & Canalisation Significance and results    Negligible effects . red. lameness o Septicaemia / Death Character Size Consistency Color Attachment Endothelium Composition Thrombus Fills vessels Dry & friable White.

right side heart and pulmonary artery embolism Types / Causes of emboli         Thrombotic emboli : Thrombo embolism – arteries (Thrombi detach to form emboli) o Heart – vegetations o Parasitic. mesenteric. Fibrin . bacteria Bacterial emboli : Septicaemia Parasitic emboli : Dirofilaria immitis .In blood transfusion. o ―Fat embolism syndrome― (Acute respiratory symptoms. when blood is improperly defibrinated / inadequate anticoagulants Fat emboli . it kills large number of organism and forms emboli on coronary vessels which is fatal.EMBOLISM  An embolus is any foreign body floating in blood. The process is called embolism. heart etc) o ―Caission‖ means .Pulmonary artery – dog o Schistosomes – Portal. tissue fluid and fat o If the worker surfaces suddenly i. Nasal blood vessels o Trypanasomes – If tartar emetic is given rapidly. tachycardia neurological symptoms) Air or gas emboli o Incision of large neck veins (surgery / suicide) o Air sucked into veins Embolism o In criminal abortion Pumping air into uterus o Air in large uterine vein o Emboli o Enters circulation o Heart o Foamy blood o Acute heart failure – Sudden death Caission's disease o Humans o Sudden change in atmospheric pressure o Under water construction workers o Deep sea / scuba divers o Unpressurised aircrafts ascends rapidly o Under water construction workers o Increase air pressure within under water compartment to compensate water pressure o Breathing o Increase air dissolve in blood. o Filarial .In fracture of long bones. N2) o O2 and CO2 are soluble and cause no harm.water tight chamber used underwater o Also called ―BENDS‖ – severe cramping pain .e decompresses o Dissolved gases come out as bubbles (O2. fat in the marrow cavity gets dislodged and forms emboli.Lymphatics emboli in brain Neoplastic emboli : Clumps of tumour cells in circulation producing metastatic tumours. venous embolism is common Thrombus in leg vein may form emboli to reach large blood vessel. N2 which is insoluble form emboli o AIR embolism (Brain. CO2. These are lodged in lungs and leads to death. atherosclerotic. Location of embolism     Artery / venous / capillaries / lymphatics In domestic animals emboli always occurs in arteries In human.

coma. convulsions. Significance / Result of embolism    Character of emboli o size .large emboli → large blood vessel blocked o septic / aseptic – new foci of infection o neoplasms – metastasis Number of emboli o Increased sites of obstruction Organs involved o Liver / Lung / muscle .no collateral circulation – Infarction INFARCTION  An infarct is an area of coagulative necrosis results due to sudden blockage of an end artery which has no collateral circulation. shock. mucin. Causes Thrombus / embolus   Pressure on the vessel wall causing ischaemia o Ligatures o Decubitus ulcers o Torniquets o Tumours o Cysts / abscess o Volvulus / intussusception of intestine Contraction of vessel wall Ergot poisoning  .Large blood supply o Very little effect o Heart / Kidney / Spleen .  Clumps of normal of normal body cells o Occurs when tissue / organ is damaged Amniotic fluid embolism o Complication of labour o Infusion of amniotic fluid (Epithelial cells. cyanosis. fat. meconium) o Maternal circulation o Due to tear in placental membrane or rupture of uterine veins o Maternal mortality (Respiratory distress. death) o Rare in domestic animals .due to anatomical differences in placental / uterine structures Pradoxical emboli  Emboli that pass directly from the right auricle into the left auricle through patent foramen ovale thereby emboli originating from vein will be lodged in systemic vessels instead of being in pulmonary vessels.

Smooth muscle contraction  Narrowing of blood vessel  Ischaemia  Seen in extremities (legs. tail. ears.Fusion of RBCs into homogenous mass  . wattles)  Hypotension Shock Ischaemia Brain infarction Pathogenesis Thrombus (blocking of end artery)  Ischaemia  capillaries dilate to increase blood supply  Hypoxia Area red color [Red infarct]  Damage to endothelium  Haemorrhage  >2 hours .

Lysis of RBCs  Release of haemoglobin  Loss red color [Pale infarct]  Inflammation  Scar (yellow / brown due to haemosiderin Macroscopical appearances   Red or pale in color Cone shaped – apex of cone is at the point of obstruction of vessel . streptococci o Cows – very common – emboli of uterine vein after parturition Infarcts of spleen .Coagulation necrosis of cells  72hours . depressed areas Causes o Cardiac vegetations – Corynebacterium pyogenes.Degeneration of cells  24hours .base towards periphery Infarcts of kidneys         Common in cows and pigs Yellow or pale Wedge shaped – seen in cortex Apex at arcuate arteries Base at capsular end of cortex No capsular necrosis Appears as healed.

strangulation  CVC  Necrosis  Gangrene  Sequelae o Fatal o Toxaemia o Shock o Peritonitis Infartion of brain        Common in man Due to arteriosclerosis Animals – Dogs – automobile accidents Cerebral infarction Softening → Myelin engulfed by microglia – ― Compound granular corpuscles‖ Organization or cyst formation (neuroglial cells) Cyst with yellow fluid ―Apoplectic cysts‖ Infarcts of heart      Common in man due to arteriosclerosis Not seen in animals Red or pale Healed infarcts – Scar Sequelae of cardiac infarcts – Myomalacia cardis Infarcts of liver .    Pale or red color Seen in borders But in dogs. it is band like Due to cardiac thrombi Infarction of intestines     Common in horses – anterior mesenteric artery (Strongyle worms) Whole surface of bowel is affected Red in color Causes Volvulus. intussuception.

depression animals General anaesthesia . heart. intestine) – SHOCK/ Toxaemia/ Septicaemia SHOCK  A common grave medical emergency characterized by a reduction in effective circulating blood volume and in the blood pressure. Definition   Shock (cardiovascular collapse) is a circulatory dishomeostasis associated with loss of circulating blood volume and reduced output and or inappropriate peripheral vascular resistance. Causes of shock          Trauma / burns Profuse haemorrhage Bacterial septicaemia Myocardial infarction (man) Pulmonary embolism (man) Psychic stimuli (man) Crushing injuries (automobile accidents) in dogs Cold. Causes o o o Tumours Thrombus due to Clostridium hemolyticum in bovines Red in colour Infarcts of lungs     Common Cone shaped Red color Causes o Emboli from o Cows – Uterine veins & posterior vena cava (Abscess) o Horses – Mesenteric veins o Pigs – Pulmonary veins (Hog cholera) o Hypostatic congestion o Chronic venous congestion o Cattle and sheep – Pasteurella infection → Pulmonary infarction (Haemorrhagic septicaemia) Sequelae of infarcts    Organization and scar formation Gangrene Death (Brain. exhaustion.e. Although causes of shock can be diverse the underlying cause of shock are relatively stereotyped i. hypoperfusion.

Secondary shock It is fatal Causes of shock 1. neurogenic impulses causes vasodilation and blood pressure decreases which leads to cerebral ischaemia and results in loss of consciousness (Pallid face. fainting)     Appears immediately after extensive injury Nervous stimuli in which widespread paralysis of capillaries occurs Animals o Rough handling of animals o Undue manipulation of intestine in abdominal surgery Humans o In psychic state like fear. slow breathing.Classification of shock   Primary shock Secondary shock Primary shock (Syncope. Reduction in blood volume o o Loss of blood from injuries (Haemorrhages) Loss of fluid into injured tissues  Severe burns  Crushing injuries Oedema  Vomition  Diarrhoea Dehydration  Na deficiency  Addison‘s disease Dehydration . excitement and apprehension. feeble pulse) o Transient / Patient recovers with rest.

Loss of about 10% blood volume can occurs without consequence. The effective circulating blood volume is decreased. Pulmonary embolism and pulmonary or aortic stenosis o Other cardiac dysfunction Unsuccessful compensation leads to stagnation of blood and progressive tissue hypoperfusion. bleeding wounds  Bacterial toxins  Burns. cardiac tamponade Pulmonary embolism → No circulation → Shock Classification based on fundamental underlying problem    Cardiogenic shock Hypovolumic shock Blood maldistribution shock o Septic shock o Anaphylactic shock o Neurogenic shock Cardiogenic shock results from failure of heart to adequately pump blood. mustard gas. The systemic vascular dilatation results may dramtically increase microvascular area and although the blood volume is normal. ANTU) 2.   Immediate compensatory mechanisms to increase vascular pressure o Vasoconstriction and fluid movement into plasma. Hypovolumic shock arises from reduced circulatory blood volume due to blood loss caused by haemorrhage of fluid loss secondary to vomiting. pain.g. Blood maldistribution shock is characterised by decrease peripheral vascular resistance and pooling of blood in peripheral tissue. fear. This leads to decreased vascular permeability and tissue hypoperfusion. but when blood loss approaches 35-45% blood pressue and cardiac output can fall dramatically.  Diabetic coma Poisons (Phosgene. Capillary bed dilation o Decreased cardiac output → decreased blood volume  Neurogenic Stimuli  Anxiety.   This occurs due to o Myocardial infarction o Ventricular tachycardia o Fibrillation or other arrhythmia o Dilating and cardiac myopathy o Obstruction of blood flow from the heart  e. diarrhoea or burns. crushing injuries  Anoxia 3. . Acute circulatory failure o o Infarction.

release of histamine and systemic vascular dilatation. Pathogenesis of shock  Ischaemic shock Septic shock . o Causes  Exposure to insect or plant allergen. o Here components of bacteria or fungi (endotoxin.  Drugs  Vaccine Interaction of an inciting substance with Ig E and mast cell results in mast cell degranulation. a lipopolysaccharide within the cell wall of gram negative bacteria) which are released from degenerating bacteria is potent stimulus and causes for septic shock. increased vascular permeability and tissue hypoperfusion.  Neurogenic shock o Causes  Trauma (particularly nervous system)  Electrocution (Lightening stroke)  Fear  Emotional stress Here autonomic discharge that results in peripheral dilatation followed by venous pooling of blood and tissue hypoperfusion. When compared to anaphylactic and endotoxic shock wherein cytotoxic plays a major role in intial peripheral vascular dilatation. Anaphylactic shock is generalised type I hypersensitivity.  Septic shock o Common type of shock associated with blood maldistribution.

Vasoactive principles .

anuria. recumbent.Acute tubular necrosis Lungs o Resistant to hypoxic cell injury o Not affected in hypo volumic shock o But changes seen in endotoxic or neurogenic shock GIT – patchy mucosal haemorrhages ―Haemorrhagic enteropathy‖ Liver – Fatty changes / central necrosis . weak pulse rate Cold extremities Anxiousness Shallow breathing Microscopical appearance      Venules and capillaries engorged with blood Fat embolism in lungs – traumatic shock Fatty degeneration and necrosis in liver / heart Renal tubular necrosis – casts in tubules Adrenal cortex is foamy.Symptoms of shock     Lethargy.decreased BP → Anoxia → Neuronal degeneration ↓ Encephalomalacia ↓ Death  Pulmonary infection – Pulmonary oedema → Bacterial growth Morphology of shock        Hypoxic cell injury Brain – Neurons – reversible cell injury o Irreversible cell injury (ischaemic encephalopathy) Heart – Subpericardial / Subendocardial haemorrhages and necrosis Kidneys . due to depletion of cholesterol Significance and results      Recovery – on blood transfusion / supportive treatment Death – irreversible shock Renal insufficiency o Oliguria. uraemia o Pigment casts in tubules o Inflammatory oedema compresses renal parenchyma o Ischaemia – due to vascular collapse o Tubular degeneration and necrosis Cardiac failure Cerebral ischaemia .

lungs. increase in weight when involves all cells in the organ.Chicken . heart Pulmonary oedema and congestion Kidneys enlarged. It is the first change to all forms of injury to the cell. kidneys.Swollen kidneys . The organ is swollen. It is difficult to appreciate the change with light microscopy. Acute cell swelling . intestines Petechiae on serous surfaces Fatty changes ← necrosis in liver.organs appears pallor. increase in turgor. kidney.Macroscopical appearance         Haemorrhages – Pale tissues Increased vascular permaeability – Oedematous tissues Passive congestion of liver. red – blue pyramids Adrenal cortex – brilliant yellow – early stage reduced size / Pale – Later stage ACUTE CELL SWELLING This occurs whenever the cells are incapable of maintaining ionic and fluid homeostasis. pale cortex. Causes  As discussed in the reversible cell injury Grossly.

e. Mucin is glassy. enlargement of cells is mostly observed in liver. hepatic sinusoids and capillary network inrenal cortex. Hydropic degeneration A variant of cell swelling with excessive accumulation of fluid leading to even bursting of cells. It is caused by more severe irritant.g. Cytoplasm shows vacuoles which represent distended and sequestrated segments of endoplasmic reticulum. Causes      Physical causes o Rubbing o Friction injury o Axe handling o Ill fitting shoes Thermal injuries o Fire accident o Hot substances – water and oil o Blisters are seen.e. vacuoles with water are identified. slimy glycoprotein normally produced by epithelium cell lining mucous membranes. Invasion of pyogenic bacteria like Streptococci and Staphylococci may cause abscesses or septicaemia. Mucinous or mucous degeneration Mucinous or mucous degeneration is the excessive accumulation of mucin in degenerating epithelium cell. Fluid escapes on incision and blister collapses consequent. rediodide of mercury Infectious agents o FMD in cattle – vesicles o Pox – blisters in stratified squamous epithelium Neoplasm o Cervical cancer Grossly. Mucus is mucin mixed with water. Sequelae  Healing occurs rapidly in uncomplicated cases without scar formation. It is discernible by compression of microvaculature of organs. staining of fat or glycogen. Eosin stains pink depending on protein content. blisters are seen onskin.or in skeletal and cardiac muscle. Using negative method of staining i. Microscopically. stringy. Cells may enlarge with coalition of fluid and may burst showing blisters and vesicles. cells are swollen. viscid. Chemicals o Application of croton oil.Microscopically. convoluted tubules of the kidney. Cytoplasm stains slightly more eosinophilic and more granular than normal. . Prickle cell layer is affected.

Haematoxylin stains the mucin blue. bovine viral diarrhoea Grossly. Causes    Neoplasm of connective tissue e. e. Mucosa is hyperaemic. Pseudomucin is not harmful and secretion of a normal cell. parasitism or chronic disease Grossly. Sequelae  In cachexia. starvation. cytoplasm shows small droplets of mucous which may coalesce forming large droplets displacing nucleus to side and compressing the nuclei. flaccid in consistency and has translucent jelly-like appearance. In oestrus. Pseudomucin is not precipitated by acetic acid and stains pink with eosin whereas mucin is precipitated by aceticacid and stains blue with haematoxylin. Tumours indicate embryonal nature and it isunfavourable. common cold. Microscopically. Mucicarmine and PAS stains the mucin red. Mechanical or chemical injury (Disinfectant or soap). Infectious diseases – Canine distemper. Thermal injury by heat or cold. Sequelae  On removal of the causative agent. Microscopically. As the mucin accumulation continues the cell ruptures and desquamated. flabby. Affected tissue is shrunken. the fat becomes normal on correction of condition. mucous covering is seen as clear transparent material on mucous membrane which is stringy and slimy inconsistency. Hyaline degeneration (Hyaline change) . large amount of mucous is normally produced which may be hanging from vulva of cattle. nuclei are hyperchromatic and intercellular fluid takes slight bluish tinge. degenerated tissue stains intensely blue with haematoxylin.g.Myxoma and myxosarcoma Thyroid deficiency in human –myxoedema Cachexia. Mucoid or myxomatous degeneration Mucoid is a glycoprotein similar to mucin in connective tissue found in foetus but not in adult tissue.Causes     It is caused by mild irritant.g. adipose tissue shows the change. Pseudomucin which resembles mucin degeneration is secreted by ovarian cystadenomas and parovarian cysts. epithelium lost is repaired by regeneration following stoppage of overproduction of mucin.

saddles andharness o Papillomas in dogs and cats o Chlorinated naphthalene poisoning in cattle causes hyperkeratosis o Hypovitaminosis A –keratinisation of epithelium of digestive and upper respiratory tract May be protective but the condition like corns may be very painful.g.e. Pathological amounts of keratohyaline o Mechanical injury . Cellular hyaline  The dead cells are kneaded together forming homogenous mass resembling sand.They are observed in lungs in pneumonia. Affected tissue appears homogenous glassy and pink in H & E staining. in brain as brain sand. Gout    This is mainly observed in birds in which the end product of protein metabolism is uric acid (insoluble inwater) and is produced in liver. There are two types of gouts o Visceral gout o Articular gout Causes It is mainly due to   Failure of urinary excretion of urates o Obstruction of ureters o Renal damage o Dehydration (common with water deprivation) Hypovitaminosis A . urea is the end product of protein metabolism which is water soluble. Mammals are ureotelic organisms i. Connective tissue hyaline  This is found in old scars. degenerating stroma of tumours. Removal of the cause results in desquamation of excessive keratohyaline and epithelium becomes normal.e.hyaline – glassy) It is the descriptive terminology of microscopical appearance. pulmonary infarction. mammary glands of cows which are dried off quickly.    Keratohyaline Cellular hyaline Connective tissue hyaline Keratohyaline    It is normally found in stratum corneum. lymph nodes in chronic inflammation and arteriosclerosis. since it stains with iodine it is called corpora amylacea (Starch-like). The gout is defined as increase in the amount of deposition of uric acid and urates in tissue (viscera and joints). This is permanent change persisting for life. They are commonly seen in prostate. in islets of Langerhans in diabetes and in renal nephritis as the renal tubular epithelium gets desquamated and forms hyaline cast with albumin. It may be found in different conditions.(L.

weakness and neurological signs due to hypoglycaemia and growth retardation and progressive hepatomegaly is found as they develop. air sacs and peritoneum and in severe cases deposition are found in the synovial sheath. It may be associated with prolonged hyperglycaemia and there may be lack of enzymes that metabolize carbohydrates. Hence. Articular gout  It is a sporadic problem. The condition is not common in animals. The cells are swollen with foamy cytoplasm. On H & E section. This condition is reported in dogs and cats. The joints are enlarged with deformed feet. Visceral gout   The deposits of urates are found in kidney. Microscopically. muscle and liver. heart. Type Ia (von Gierke disease in humans): There is deficiency of glucose-6-phosphatase that catalyses hydrolysis of glucose-6-phosphate to glucose and phosphate. Type III or Cori-Forbes' disease: There is deficiency of amylo-1. tendons. Glycogen overload may be encountered in: o Neutrophils in inflammation o Fast growing neoplastic cells o Necrotic areas o Diabetes mellitus o Liver of young and growing animals o Well-fed animals . It is a group of disease in which two forms are recognized in animals. It is surrounded by inflammatory cells like neutrophils. GLYCOGEN STORAGE DISEASES (GLYCOGENOSES)     The cells may accumulate abnormal amount of glycogen in the cytoplasm. Clinical signs  Leg shifting. it appears as clefts. cats and sheep. It is the sequel of alkalosis with protein breakdown. Tophi are characteristics of articular gout which are deposition of urates around joints particularly of the feet. joints and muscular surfaces. Massively enlarged hepatocytes show vacuolations with aggregation of glycogen rosettes.6-glucosidase which converts glycogen to glucose. Type II or Pompe’s disease: There is deficiency of lysosomal α-glucosidase with accumulation of glycogen in the lysosome of brain. This condition is seen in cattle. glycogen is stored in the cytoplasm of liver. It is found only at necropsy. skeletal and smooth muscle and nerve cells. urate crystals found in clusters which are pale elongated and needle shaped. lymphocytes and foreign body giant cells and fibroblasts.  Oosporin (mycotoxicosis) Sodium bicarbonate treatment Hyperuricaemia is the result insodium bicarbonate toxicity. It appears as white chalky coat. Deposits are seen as white semifluid substance. The condition is not a significant entity in animals as compared to humans. mesentery. serous surfaces of heart. dogs. GLYCOGEN OVERLOAD  It is excessive intracellular accumulation of glycogen with derangement in glucose or glycogen metabolism. lameness and inability to bend the toes are observed. Affected pups show tremors.

cryostat sections are used to stain fat. Chemicals like CCl4 and yellow phosphorous can also induce hepatic steatosis. the fat will be dissolved by the xylol and gives vacuolated appearance in the Haematoxylin and eosin stained sections.  Grossly. Lipidosis is more common than other conditions.        Mobilization of free fatty acids from the gut (Chylomicrons) or adipose tissue Mitochondrial injury leading to decreases in β-oxidation of fatty acids to ketones etc. (Hypoxia. but pale enlarged liver is observed in steroid induced hepatopathy. MECHANISM OF HEPATIC LIPIDOSIS It is the accumulation of triglycerides or true fats and cholesterol in the cytoplasm of parenchymatous cells. scarlech red and Oil Red O. Starvation increases triglyceride mobilisation. CCl4 poisoning and aflatoxicosis Failure to form lipoproteins Failure to release lipoproteins from hepatocytes o The last two conditions are uncommon. Glycogen stains red with PAS and Best‘s carmine staining. fat droplets are seen on the blades of knife.Yellow  Microscopically. Protein malnutrition affects apolipoprotein synthesis. Grossly . clear cytoplasmic vacuoles in the hepatocyte represent the glycogen. Upon incision. pushing the nucleus to a side. Fatty acid mobilisation from adipose tissue is common in animals following higher energy demand. changes are not usually detected. Special stans for fats are sudan III. toxins) Decreased apolipoprotein synthesis e. fluid and glycogen accumulation. Microscopically. Enlarged with rounded borders.Chicken . sample should be collected immediately after death and tissue must be fixed in non-aqueous solution like alcohol to avoid loss of glycogen since the glycogen is water soluble and glycogen is converted to glucose after death.g. soft and friable liver is found in moderate to higher grade fatty changes. pale to yellow. To differentiate from hepatic degeneration. Tissue may float in the fixatives. clear to variable sized and may also form a single large vacuole. enlarged. Hepatic lipidosis can occur from one or more mechanisms. sudan black. sudan III and sudan black imparts black colour and scarlech red imparts red colour . During the processing of fat tissue with xylol clearing. To demonstrate glycogen. Oil Red O stains fat red and while it is PAS negative. hepatocytes show vacuolations which may be small. Fatty liver .

The lysosomal dysfunction leads to accumulation of normally degraded substrates leading to death of cells.PATHOGENETIC CHANGES IN HEPATIC STEATOSIS HEAT SHOCK PROTEINS      Heat shock proteins (HSPs) are intracellular chaperones (Fr. buffering and expression of mutations. e. Stress causes protein aggregation and degradation. today‘s context to look after proteins within the cell). their presence indicate physical damage.  Examples . These are involved in protein folding. Antigen presenting cells (APC) express receptors that ligate Hsp bound antigen peptides. Combination elicited MHC class I restricted antigen specific CD8 cytotoxic T cell responses (immunity to cancers). LYSOSOMAL STORAGE DISEASE These are genetically determined diseases with reduced lysosomal enzyme synthesis and now understood that it may also be caused by other contributory factors like lack of enzyme and substrate activators. UV radiation. Hsps are not commonly present in blood and body fluids. thermotolerance. The disease kills the developing foetus or may be manifested in neonatal or early life. Hence.g. degradation of protein (Hsp 70) assembly of protein. Hsp alone or peptide alone is non-immunogenic. etc They also play a role as intracellular chaperones of antigenic peptides. an older woman who looks after a girl. Hsp 60. Hsp 90 and Hsp 70. There are about ten families. heat. e.g.

and rubbery consistency of brain are seen. Grossly. . In GM1gangliosidosis. In the central nervous system: a) deficiency of β-galactosidase in the lysosome results in GM1gangliosidosis b) deficiency of β-hexosinamidase results in GM2gangliosidosis. cytoplasm is foamy. liver or other organs. Excess GAGs in urine of weaning animals confirms this disease Naemann-Pick Type-C disease  There is accumulation of sphingomyelin in lysosomes deficient in sphingomyelinase in dogs and cats. atrophy of brain. Globoid mucodystrophy may occur in later stages with loss of myelin. whorles and laminar arrangements of membranes are seen in the CNS and other visceral organs. is caused by the absence of a-L-iduronidase in Siamese cats and Plott Mucolipidoses  There is genetic deficiency of ganglioside sialidase enzyme and consequent accumulations of glycolipids and GAGs in the form of granulofibrillar vacuoles in hounds. Microscopically. There is lack of specific hydrolases in lysosomes which results in massive accumulations of GAG polymers and formation of giant lysosomes. Mucopolysaccharidoses   The defectively degraded glycosaminoglycans (GAG) are stored in the cells that normally degrade them. The affected animals show deformities of face and bones. finely granular and vacuolated with displacement of nuclei. hepatocytes and mononuclear cells and phagocytes show vacuolations. These are genetically determined group of diseases. Mucopolysaccharidosis type I. Abnormally large granules are seen in the leukocytes. Corneas are clouded. the neurons are enlarged.o o o o Lipid storage disease Mucopolysaccharidoses Mucolipidoses Glycogen storage diseases Lipid storage disease    Lysosomes which are lacking enzymes do not degrade fat substrate in te cytosol leading to accumulation of lipid materials in the brain. The cytoplasm of nerves.

fever o Cold .Local tissue freezing. burns. high frequency current o Heat .Sun stroke.CAUSES AND MECHANISM External causes    Physical causes o Trauma by cutting objects and blunt objects o Electrical – Lightning. cold shock o Radiation .UV / X /cosmic radiations o Pressure . vitamins and minerals o Agrochemicals– nitrates o Environmental deficiency  Water –dehydration  Oxygen –asphyxia  Sunlight – forvitamin D formation (Hypovitaminosis D) o Biological toxins  Bacterial and fungal toxins  Arthropod and snake venom  Pesticides –organochlorine compounds Biological causes o Acellular – Viruses. fungi o Metazoan parasites – Trematodes.CELL INJURY AND NECROSIS REVERSIBLE AND IRREVERSIBLE CELL INJURY . prions o Prokaryotes – Bacteria. calorie.Increased or decreased pressure Chemicals o Nutritional . cestodes.mycoplasma o Eukaryotes – Protozoa. chlamydia. nematodesand insects Internal causes Genetic causes– mutation of genes to chromosomal defects The common causes of cell injury     Hypoxic injury Free radical injury Chemical injury Virus induced injury . rickettsia.HypervitaminosesA and D  Deficiency –protein.Excess / deficiency  Excess .

Events in ischaemic cell injury .

proteins.exogenous chemicals or drugs e. generation of endogenous oxidative reaction or enzymatic metabolism. e. Thesecause lipid peroxidation. Mercury binds with sulphydryl group and other proteins andcause increased cell membrane permeability and inhibition of ATPase dependant transport or indirectly by converting chemicals which are not biologicallyactive into reactive toxic metabolite that attack target cells. glutathioneand ceruloplasmin. lipids or carbohydrates. sulphur containing amino acids (cystine.g. Free radicals may be initiated in cells with radiant energy (UV /Xrays).g. The autocatalytic reactionresults in membrane damage involving rough endoplasmic reticulum.Vitamin E.Reversible cell injury is non-lethal and previously referred as degeneration. protein damage and DNA damage. Carbon tetrachloride is converted to CCl3 in hepatocyteswhich acts on membrane and generate lipid peroxides. Mostly reactive free radicals formed can induce membrane damage and can cause direct injury by covalent binding to membrane lipid and protein. mercuricchloride poisoning. Carbon tetrachloride (CCl4)poisoning. Irreversible injury causes necrosis or death of the cells.Free radicals are extremely reactive and unstable and enter into reaction with inorganicand organic substances. Chloroform. methionine). The two patterns found inreversible injury are   Cellular swelling Fatty change Free radical injury   Free radicalsare chemical species that have single unpaired electron in the outer orbit. particularly free radicals react with membrane and nucleic acid. hydrogen peroxide and hydroxide. Chemical injury  Chemicals can induce cell injury directly by reacting with critical cellular molecules e. . detachment ofribosomes. The antioxidants(endogenous or exogenous) are helpful in scavenging the free radicals e. Lipid peroxidation products can also damage plasma membraneto increase permeability to sodium and water resulting in cell swelling. They initiate autocatalytic reactions. Virus induced cell injury This may be through immune mediated reaction and direct cytopathic effect.g. reduced protein synthesis and fatty liver due to lack of lipidacceptor protein.g. carbon tetrachloride The oxygen-derived radicals are superoxide.

Oncogenic viruses which stimulates host cellreplication may produce tumours.Viruses that induce cellular changes are of two types   Cytolytic / cytopathic viruses which cause variousdegree of cell injury and cell death. .

grayish white. These are     Pyknosis: Shrinkage or condensation of nucleus which takes up deep blue colour. Karyolysis (Gr. Depending on the gross and microscopic features necrosis is divided into following four types. Coagulative necrosis . dull and depressed surrounded by hyperaemic zone. rhexis-Fragmentation): Fragmentation of nucleus. Grossly. the necrotic tissue is dry. Microscopically. Lysis-Dissolution): Dissolution or disappearance of nucleus. white or grayish white and homogeneous and slightly depressed from the surrounding healthy tissue. necrosis of liver in Fusobacterium sphaerophorus infection. Grossly. mercuric toxicity in renal tubular epithelial cells and cutaneous or mucosal epithelium in contact poison with phenol. the structural details are lost due to necrosis‖ This type of necrosis occurs due to ischaemia. nuclear changes are characteristic. The chromatin condenses to a structureless mass Karyorrhexis (Gr. Cytoplasm is swollen. Karyo-Nucleus. Nekrosis-Deadness) is defined as death of cells in a living vascularised tissue or local death of cells in a living animal. whit muscle disease in vitamin E and selenium deficiency. necrotic tissue is pale.NECROSIS Necrosis (Gr.     Coagulative necrosis Caseation necrosis Liquefactive/suppurative necrosis Fat necrosis Coagulative necrosis   ―While architectural details of tissue are retained. homogeneous and stained intensely pink due to decreased basophilia with loss of ribosomes. Karyo-Nucleus.

grayish white cheesy granular mass. Caseous necrosis (L. . amorphous necrotic area surrounded by epithelioid cells. Caseous necrosis . giant cells. It is especially seen in the central nervous system (malacia) and any infection with pyogenic bacteria leading to pus formation (Abscess). oesophagostomosis and caseous lymphadenitis in sheep and tularaemia in primates. lymphocytes and plasma cells with central area of dystrophic calcification Liquefactive necrosis Necrotic tissue is liquid in consistency. The later is due to autolysis or heterolysis from enzymes of neutrophils leading to collection of pus containing necrotic tissue. The dead tissue attracts calcium deposits and is enclosed within a connective tissue capsule. the necrotic tissue is converted into a homogeneous.Tuberclosis . Grossly. karyorrhexis and karyolysis or absence). the architectural details of the area is maintained and cellular details are lost. This type of necrosis occurs in Mycobacterium tuberculosis infection. The cytoplasm appears homogeneous and eosinophilic due to coagulation of protein. The cellular shape is preserved and nuclear details are lost (Nuclei show pyknosis. It takes long time for the removal of dead materials because the autolytic enzymes are destroyed and no leukocytic responses.Lung Microscopically. liver and muscle except the brain. structure less. friable.Cheese)  The architectural and cellular details are lost. This is more chronic type of lesion often associated with poorly degraded lipid materials of bacterial origin. soft. This is due to blockage of proteolysis with denaturation of proteins including enzymatic proteins of the cell. This type of necrosis is characteristically found in parenchymatous organs like kidney.Microscopically. Caseous . The former is due to severe hypoxic or toxic injury with focal dissolution of the neuropil.

Fat solvents do not remove necrotic fat. contracted and agranular neutrophils with varying amounts of tissue debris. Microscopically. The pus becomes caseous and insipid if stands for longer time. An abscess is a localised collection of pus (Liqefactive necrosis) caused by suppuration. The fat loses yellow translucent nature. the lipase released from acinar cells gets activated and saponification occurs by digestion of triglycerides into glycerol and fatty acids. Glycerol being water soluble. necrotic adipocytes may show eosinophilic shadow outlines.microorganisms and dead neutrophils (Suppuration). fibrin and plasma proteins. become basophilic due to dystrophic calcification and surrounded by inflammatory reactions along the area due to acute to chronic injury. hard. The pyogenic organisms cause localized necrosis and attract neutrophils to the necrotic areas. The process is designed to contain the pathogenic organisms and sequestering necrotic tissue from spreading in the animal. deep in tissues. white. This is a part of inflammatory response. Liquefactive necrosis . e. .In acute pancreatic necrosis and pancreatitis. the pus or the purulent area shows dark.g.Pyometra Microscopically. is absorbed. Grossly. Fat necrosis It is death of adipose tissue in a living animal. opaque masses resembling that of soap flakes are seen. The released fatty acids when combine with calcium results in the presence of chalky white flakes. Pancreatic fat    Pathogenesis . There are different types of fat necrosis Enzymatic fat necrosis It is commonly found in steatitis (Inflammation of fat) and other inflammatory lesions affecting adipose tissue.

Microscopically. APOPTOSIS Programmed cell death in which there is death of individual cells without inciting inflmmatory processes. Calcified area is basophilic. e. omental and retroperitoneal fat show necrosis containing large masses. necrotic adipocytes are pale pink (eosinophilic) and show numerous clubs (fatty acids) and crystals. Stenosis of intestine may occur in extreme cases. surrounded by chronic inflammatory cells.g. biting. Example: Surgical injury to subcutaneous fat.    Causes : working. physiologic cell death occurs which may be referred as programmed cell death or apoptosis. Mechanism of Apoptosis There are two processes:   Initiation phase mediated by caspases Execution phase in which enzymatic degradation leads to cell death Initiation phase There are two pathways of initiation of apoptosis:   Extrinsic receptor initiated pathway Intrinsic mitochondrial pathway These two pathways are interconnected and converge to activate caspases . parturition (perivaginal fat in cattle. opaque. chalky masses found in the area with acute to chronic inflammatory reaction. and fatty acid crystals dissolve in fat solvents leaving clefts.Traumatic fat necrosis It results from mechanical injury to adipose tissue. firm. injury to vagina during dystocia and abdominal fat necrosis in cattle Mesenteric. The derivatives of fat.    Grossly. Tuberculosis and Johne‘s disease in cattle and sheep. necrotic fat is opaque. Nutritional fat necrosis This is the result of necrotic alteration in fat associated with extreme emaciation. subcutaneous and intramuscular fat in recumbent cattle) Grossly. foamy and chalky white and may be calcified. Differential diagnosis: Inflammatory reaction and calcification are lacking in autolytic fat. glycerol dissolves in body fluids. In embryogenesis and normal growth. Apoptosis can also occur in pathologic diseases.

cytoplasm is dense and organelles are tightly packed. These caspases can act on many cellular components like cytoskeleton and nuclear matrix proteins. caspase-8 and 9 are initiator caspases and caspase-3 and 6 are executioner caspases. The complex activates caspase-9. Caspase target proteins of transcription. Intrinsic mitochondrial pathway: There are more than 20 antiapoptotic proteins. Histopathologically.g. Condensation of chromatins: Most characteristic in apoptosis. The enzymatic death programme sets in motion by rapid and sequential activation of other caspases. Not only gross changes. Bcl-2 and Bcl-x are replaced when cells are deprived of survival signals or stress by proapoptotic members like Bak. cytochrome C from mitochondria which binds to Apaf-1(Apoptosis activating factor-1protein). These activated caspases trigger a cascade of caspase activation and mediate execution phase of apoptosis.g. Cytoskeleton destruction and nuclear break down occurs. DNA replication and DNA repair in the nucleus e. This leads to increased mitochondrial membrane permeability and release of several proteins which activate caspase cascade e. Aggregation of chromatins under nuclear membrane with variable shape and size (Semilunar shape) Cytoplasmic fragmentation Cytoplasmic buds containing fragments of nucleus: Cytoplasm shows excessive surface budding and formation of membrane bound fragments (Apoptotic bodies) containing cytoplasm and tightly packed organelles with or without nuclear fragments.g. but microscopical changes are also not obvious since single cell death occurs. . caspase-3 activates cytoplasmic DNAs. These caspases are hydrolysed autocatalytically following cleavage of initiator caspase to generate the active form. Execution phase    The final proteolytic cascade is mediated by the proteases (Caspase: ‗c‘.       Shrinkage of individual cells: cells-size smaller. Of which Bcl-2 and Bcl-x are located on the mitochondrial membrane of cytoplasm. Nucleus itself may break up into two or more fragments Presence of apoptotic bodies in the adjacent cells and phagocytes Inflammation is absent. There are more than 10 members in caspase family which are grouped into initiator and executioner groups depending on their order in which they are activated during apoptosis e.  Extrinsic pathway: On cross linkage of Fas (Death domain) by its ligand three or more molecules come together and bind to cytoplasmic Fas-associated death domain (FADD) which in turn binds to inactive forms of caspase-8 via death domain. FLIP protein inhibits apoptosis by binding to procaspase-8. Apoptosis activating factor from mitochondria also neutralizes various apoptotic inhibitors which block caspase activation. This mechanism is used to protect infected normal cells from Fas mediated apoptosis.cystine protease that cleaves aspartic acid residues). Bax and Bim.

skatol and putrescent amines-like ―putriscience and cadaverine‖. liver.rapid in onset. After death. Retina-most sensitive. 2. normally present in faeces. indol. By a careful study of a postmortem changes one can determine the probable time of death and this is of great importance in medicolegal cases. which a pathologist must have knowledge of to distinguish them from lesions found in disease. 5. 4. testis-abdominal organs also show autolytic changes. leads to pronounced postmortem changes in the body like gaseous distension. 1. 3. 9. enzyme secretions and the availability of moisture and substrates influence the rate of postmortem autolysis. the animal is said to have undergone somatic death. Adrenals. Pancreas-high amount-rapid changes. Post mortem autolysis Absence of inflammatory reaction Autolytic changes are seen uniform throughout the tissue Necrosis Presence of inflammatory reaction Diffuse or focal adjacent living and dead tissues are seen. Putrefaction Decomposition of tissues brought about by the protein splitting anaerobic saprophytic organisms. separates from choroids. Bacterial flora present in GIT and respiratory tract bring about the post-mortem changes rapidly under favourable conditions. Algor mortis Rigor mortis Livor mortis. 7. Fibrous tissue-less amount-slow changes. 2. 8. Horse-dry and firm muscle-slow in onset Organ involved: the degrees of the expression of postmortem changes vary from tissues to tissues. The tissue turns black or dark-green as a result of formation of iron sulphide from break down haemoglobin. Factors influencing the rate of postmortem autolysis Species of animal: Pig-soft and moist muscle.ammonia.MORTEM CHANGES Somatic death      Somatic death is the death of the body as a whole.No. hydrogen sulphide. When respiration and cardiac action have stopped. 6. The common putrefactive organisms are Clostridium spp.PM CHANGES AND GANGRENE POST MORTEM AUTOLYSIS AND NECROSIS S. softening etc. Sequence of postmortem changes 1. The presence of bacterial flora.hypostatic congestion PM clotting of blood Imbibition of hemoglobin Imbibition of bile PM desquamation PM softening PM discoloration . the cells undergo certain changes (post mortem changes). POST . results in the formation of gas and variety of foul smelling substances.

10. PM distention 11. PM displacement 12. PM rupture of organ and tissue 1. Algor mortis
      

Algor mortis is cooling of the body. It commences at or before the stoppage of blood flow. The rate of cooling depends on the following factors: External atmospheric temperature Air currents The thickness of hair coat or wool Adiposity of the animal Amount of fermentable ingesta in the digestive tract Larger animals cool slowly; so also in sheep, with thick wool cooling occurs slowly. Limbs and other extremities cool more rapidly than the trunk. The rate at which post mortem changes takes place depends on the rate of cooling and other factors detailed below:

A. Surrounding atmospheric temperature

Since the postmortem changes are brought about by enzymatic and bacterial activity, high temperature that accelerates this activity will naturally bring on the post mortem changes soon. So in summer, the carcass putrefies quickly. Cold on the other hand retards the enzymatic and bacterial activity. Freezing and deep freezing may stop the activity completely. Hence, carcasses are in perfect state of preservation under polar ice-caps for considerable length of time.

B. State of the body at the time of death

Higher the temperature at death, sooner do postmortem changes commence.

C. State of muscular activity of animal prior to death

In animals, that have been very active prior to death post mortem changes commence quicker. This is found in animals that die in chase. Similarly, animals that are killed or die of strychnine poisoning and in animals that die of tetanus, postmortem changes appear early.

The reasons are
  

higher body temperature greater production of lactic acid in muscular contractions and exercise Size of animal

Since body cools slower and so heat is retained longer in larger animals, postmortem changes appear quicker in them E. External coverings
   

Since thick hair or wool retard heat, dissipation, postmortem changes are seen sooner in thick haired or coated animals Fatness of animals Fat is a poor conductor of heat and so heat loss in fat carcasses is slow, with resultant speedier onset of postmortem changes. Infection of animals

Widespread bacterial infection, especially septiceamic in character, at the time of death begins on postmortem changes earlier.

The following are the changes noticed after death: 2. Rigor mortis Rigor mortis is contraction of muscles after death. This is a contraction of muscles after death so that the joints become stiff and body is rigid. Rigor mortis develops first in those muscles that are very active. e.g heart, palpebral muscles, muscles of the head and neck. Gradually other muscles of the forelimbs, the trunk and the hind limbs, are affected in that order. It passes of also in this order, starting first in the head. Usually, rigor mortis appears in 1 to 8 hrs after death and may disappear from 20-30 hours. The following factors hasten the onset of rigor mortis.
   

High atmospheric temperature Active exercise- hunting, fighting, racing or struggling Strychnine poisoning FTetanus

Causes of rigor mortis

The exact mechanism is not known. After death, there is a great overturn of high energy phosphate bonds in the muscle. Adenosine triphosphate (ATP) which breaks down is resynthesized by the energy derived from glycosis. So long as ATP is present, rigors do not occur. With the exhaustion of glycogen, all of ATP is degraded and rigor occurs, since in the absence of ATP relaxation of muscles cannot occur. For the relaxation of the muscles to occur, a considerable quantity of ATP must be absorbed to the muscle proteins. Hence onset of rigor is delayed in well fed animals with large quantities of stored muscle glycogen. But in starved animals, rigor naturally commences earlier. Subsequently when there is no longer any energy necessary for keeping up the chemical activity in the muscle fibres, rigor passes off. Onset of rigor mortis is slow in cold weather and in emaciated and cachectic animals. In the later, it is due to the complete exhaustion of chemical systems producing energy.

3. Livor mortis: Hypostatic congestion is, due to gravity, accumulation of blood in vessels of organs that are found on the lower side of the recumbent animal. 4. PM clot is the coagulation of blood in the vessels after death. Chicken fat is the white clot while current jelly clot is the red clot seen in the clot. PM clot is formed after death of animal.

PM clot

Cow - Heart - PM clot

5. Imbibition of hemoglobin: PM staining is pinkish discolouration of endothelium of larger vessels due to haemoglobin (liberated from lysed erythrocytes) after death. 6. PM imbibition of bile is the yellow pigmentation of the tissue occurring in the vicinity of gall bladder. 7. PM softening is softening of tissues, after death, by the action of autolytic enzymes of the cells and the proteolytic ferments of the saprophytes and infecting bacteria. 8. PM discoloration: Pseudomelanosis coli is staining (blackish / greenish discolouration) of intestines due to formation of iron sulphide (H2s + Fe from Hb = Iron sulphide) after death of animals. 9. PM bloat / PM emphysema is accumulation of gas in the rumen and intestines due to fermentation of food after death. 10. PM displacement of organs: This may occur following handling of carcass by rolling etc. 11. PM rupture of organ and tissue: This may be attributed to softening and handling but devoid of any inflammatory reaction. In equine practice, stud fee is payable only on the birth of a live foal. So, the veterinarian may be required to certify as to whether a foal was born alive or dead. The two criteria to be looked for are:

Does the lung float in water? If it floats the foal was born alive since presence of air renders the lung buoyant. Air can be present in lung only if the animal had breathed and breathing can occur only if the foal was born alive.

Types of gangrene  There are three types of gangrene o Dry gangrene o Moist gangrene o Gas gangrene Dry gangrene Dry gangrene represents an area of coagulation necrosis resulting from infarction followed by mummification. temperature and moisture. shrivel (dehydration) and brown to black (due to formation of iron sulphide: iron from haemoglobin degradation. GANGRENE Definition  Gangrene is a necrotic area invaded by saprophytic organisms leading to putrefaction. o Fescue poisoning o Cold (Frost bite): Direct freezing and ice crystal formation leading to cellular damage. The extremities of the body like tail. at the junction of living and dead tissue. sulphide from putrefaction). there is a line of demarcation due to active inflammatory reaction. ears. legs and udder are affected. proliferation of bacteria due to unfavourable environment. o However. vascular damage and ischaemic necrosis.  Causes Toxins (phytotoxins and ergotoxins): The toxins cause marked peripheral arteriolar vasoconstriction and damage to capillaries leading to thrombosis and infarction. Gross pathology o Affected part is dry (dehydration due to exposure to environment). Did it suckle? Presence of milk or curds in the stomach is valid evident that the foal was alive at birth and had suckled. o  Dry gangrene Moist gangrene .

serosanguineous exudates and gas bubbles are seen CALCIFICATION Calcification is abnormal deposition of calcium salts in tissue other than bone. Calcium if deposited in an abnormal tissue with normal or abnormal blood calcium level is considered as pathological condition. ammonia and mercaptanes. Examples: Clostridium perfringens.  Causes: Intestine desplacements: Intususception. incarceration Gross pathology o The affected parts are soft. contain gas bubbles. Gas gangrene Anaerobic bacterial proliferation producing toxin and damaging the tissues. Clostridium septicum introduced by penetrating wounds. Later liquified due to rapid proliferation of bacteria and infiltrating neutrophils. .   Gross pathology o Affected parts are dark red to black. The Clostridia chauvoei spreads haematogenously from the intestine and lodges in muscle which requires some injury and necrosis for the spores to germinate and bacteria to proliferate. bacteria.The clostridia proliferate in necrotic tissue under anaerobic environment and produce toxins which cause tissue damage. moist and reddish brown to black. There is no line of demarcation between live and dead tissue.Intussusception  Histopathology o Initial coagulation necrosis with a few bacterial multiplications. Histopathology o Coagulative necrosis of muscle. Moist gangrene . volvulus. foul smelling or putrid odour due to hydrogen sulphide. The environment is conducive for rapid growth of bacteria.  Calcium is normally present in blood and deposited in bones. serosanguineous exudates and foul smelling.

Lungs-CO2. Dystrophic calcification Dystrophic calcification is calcification of abnormal tissue with normal blood calcium levels. hypophosphataemia and withdrawal of calcium from bones. e.e. hypophophosphaturia. parathyroid stimulation and hypercalcaemia. o Renal disease with retention of phosphate. gritty mass and on section gritty sound is heard. Usually lesions are microscopical.g. o Nutritional cause with high vitamin D intake resulting in increased absorption of calcium.g. . Calcifies nodule . dead parasites.TB . Gross lesions o Hard.e. o Primary and secondary bone tumours cause rarefaction of bone. Necrotic tissues (Tuberculous lesion. Pathological calcifications are o Metastatic calcification o Dystrophic calcification Metastatic calcification   Deposition of calcium occurs in soft tissue following increase in the blood calcium (Hypercalcaemia i.mesenteric lymph node  Microscopic lesion o Calcified areas take up a blue colour with H&E stain and black with von Kossa stain o . The phosphates from the dead tissues form the nidus.12 mg/dL). Stomach-HCl. Kidneys-Hippuric acid. depression of calcium. scar tissue. Hypercalcaemia may arise due to o Parathyroid tumour in which high levels of parathormone favours phosphate excretion through kidneys (hyperphosphaturia). Wherever acid is secreted calcium deposition occurs. suppurative lesion. the calcium combines with phosphates to form calcium soaps . old thrombi   Pathogenesis o Deposition of calcium occurs around the nidus. atherosclerotic plaques. Further. renal tubular epithelial cells in mercurial poisoning).

JAUNDICE
 

Jaundice (French – yellow: icterus - Greek – jaundice). Jaundice is not a disease, it is a sign. Jaundice is defined as yellow discolouration of skin, sclerae, mucous membranes and internal organs caused by an increase in bilirubin concentration in tissues. To understand jaundice, it is essential to know the bilirubin production.

Jaundice - Icteric - Subcutis

Causes of jaundice
   

Overproduction of bilirubin due to increased haemolysis. Reduced uptake in liver, impaired conjugation (lack of enzymes) Impaired intrahepatic secretion due to hepatic damage, intrahepatic cholestasis due to biliary obstruction Impaired extrahepatic secretion due to obstruction - Due to bileduct obstruction.

Jaundice is classified into
  

Haemolytic or prehepatic jaundice Toxic or intrahepatic jaundice Obstructive or posthepatic jaundice

Haemolytic or prehepatic jaundice

Causes Bacteria : Clostridium haemolyticum, Leptospirosis Virus : Equine infectious anaemia Protozoa : Babesiosis, Anaplasmosis, Haemobartonellosis, Trypanosomosis Nutritional : Phosphorus deficiency - Post parturient haemoglobinuria Phytotoxins : Resin, Saponin Animal toxin : Snake venom Chemicals : Copper, selenium toxicity in sheep Icterus neonatarum, incompatible blood supply Pathogenesis o Excessive haemolysis results in production of greater amount of unconjugated bilirubin. Since there is a rate limiting, all unconjugated bilirubin cannot be converted to conjugated bilirubin. Hence, some amount is left in the blood. Since large amount of conjugated bilirubin is formed, it stains faeces yellow. When excess quantity of urobilin is formed (faeces intense yellow colour) and is also responsible for abnormal intense yellow urine.
o o o o o o o o

Toxic or intrahepatic jaundice

Causes
o o o o

Bacteria : Leptospirosis, Salmonellosis Virus : Infectious canine hepatitis Phytotoxins : Senecio, crotalaria Chemicals : Phosphorus, chronic copper poisoning, chloroform, carbon tetrachloride. Pathogenesis o When heptocytes are necrosed, the liver is not able to convert normally formed unconjugated bilirubin. Since the degenerated cells are swollen and disorganised and biliary capillaries are blocked, conjugated bilirubin escapes into sinusoids and enters general circulation and excreted through urine. Hence, blood contains both conjugated and unconjugated bilirubin.

Obstructive or posthepatic jaundice

Causes
o

Blocking of bileduct from within  Ascaris lumbricoides in swine  Thysanosoma astiniodes (fringed tape worm)  Fasciola gigantica in cattle

 Gall stones Pressure on bile duts from outside  Tumours, abscesses, granulomas, fibrosis, enlarged pancreas or lymph nodes o Inflammatory processes in biliary system  Cholangitis, cholecystitis – fascioliasis, Dicrocoelium dendriticum o Closure of bile duct orifice in duodenum  Duodenitis – thickening of mucosa Pathogenesis o The obstruction to normal flow of bile results in regurgitation of bile. In this case, the production of conjugated and unconjugated bilirubin is normal. Biliary stasis occurs due to (extra hepatic cholestasis) pressure, worms, inflammation and duodenitis. No urobilinogen is formed since bile is not entering to intestine. Faeces greasy and grey colour due to failure of fat emulsification and lack of faecal pigment. Urine is not containing urobilin. Clotting defects will occur due to failure of obstruction of vitamin K which is required for prothrombin formation. o

Chemical test for bilirubin van den Bergh test

5. 6. 4. hypertrophy. Present anaemia and blood parasite GROWTH DISTURBANCES    The disturbances in growth cover a broader spectrum of changes from no growth to uncontrolled growth. o Aplasia o Agenesis o Hypoplasia o Hyperplasia o Hypertrophy o Atrophy o Metaplasia o Dysplasia The cells respond to altered physiological or pathological stimuli by adapting themselves. Serum van den Bergh test Urine bilirubin Urine urobilinogen Feaces Liver function tests Blood Normal prothrombin time Total serum cholesterol Normal Haemoglobinuria. Hence. . the cellular adaptation to the increased demand is a state in between normal and stressed. greasy. no smell Negative Increased Increased conjugated bilirubin conjugated and unconjugated bilirubin Biphasic Present Present Normal Positive Prolonged Decreased Absent Direct Present Not present Clay coloured. 9. These changes are reflected as atrophy. While uncontrolled growth (neoplasm) is dealt separately. N o. 7. Parameters Haemolytic Toxic Obstructive Bilirubin Increased unconjugated bilirubin Indirect Not present Slightly present Intense yellow. the normal cell‘s homeostatic state may respond with cellular injury resulting in either death or adaption.Differential diagnosis of jaundice S. 8. metaplasia and dysplasia besides aplasia and hypoplasia. Cells may fail to develop or adapt to changing environment or physiological or pathological stimuli. foul smell Negative Prolonged Increased Absent 2. the other forms of growth disturbances are considered in this chapter. hyperplasia. Following an injurious stimulus or to stress. 3. 1.

Involution is the decrease in the size of the organ due to decrease in the number of cells. virus causes hypoplastic changes. drug induced hypoplasia occurs through degeneration and necrotic changes. rudimentary tissue of fat and connective tissue are present. Atrophy can be broadly classified into physiological atrophy and pathological atrophy. This developmental disturbance occurs in the embryo or foetus in utero. This may affect any organ or part of an organ. brain etc.g. lack of stimulation and decreased work load. not. Involution of thymus on attaining puberty.  Causes o o Any injury occurring in late stages of development of fetus or neonates. Hypoplasia It is the failure of an organ or tissue to attain its full normal adult size. formation) is the complete failure of an organ to develop. A: Without. The condition is incompatible with life when it involves vital organs like heart. HYPOPLASIA AND ATROPHY Aplasia  Aplasia (Gr. In the place of the organ. . Atrophy is representing adaptation to deficient nutrient supply. The phagolysosomes increase in size with lipofuscin pigment. The cells show alterations in lysosomes and inspissated protein in cytoplasm.APLASIA. Pathological changes: Organ will be smaller than adult size. It is associated with loss of cells. Atrophy   Atrophy is the decrease in the size (quantitative) or amount (numerical) of cells/tissues/organ after attaining full normal growth. Plasia: Development. caused by apoptosis. e. e. Physiological atrophy   Involution of the organs can be observed as the age is advanced. uterine involution after parturition (decrease in smooth muscle size and number) Senile atrophy: Atrophy of the organs occurs with ageing and reproductive organs like testis and ovaries are the first to show such changes.g. Genetic mutation affects proper differentiation and migration of cells in embryo.

Angiotrophic atrophy: Diminished blood supply (ischaemia. Disuse atrophy o Decreased work load: Decrease in the size of the body musculature due to inactivity as in the case of race horses. Neurotrophic atrophy: Decrease in the size of muscle fibres occurs if a nerve is severed or injured.g. There is imbalance between protein synthesis and degradation or loss of protein. Ovariectomy leads to uterine atrophy. the cells survive and are smaller in size with decreased function. Starvation of the tissue is caused by malnutrition. Hepatic atrophy can occur due to decreased portal venous blood flow. Parasitic ischaemia caused by Strongylus larvae by the occlusion of femoral artery leads to atrophy of hind limb in horses.g. o Immobilization: Skeletal muscle atrophic changes can occur in plaster casted animals. there will be decrease in the size of the myocytes. e.Sertoli cell tumour Pathological atrophy        Nutritional atrophy: This is due to starvation. Right .Left . Hyperestrogenism associated with sertoli cell tumour results in seminiferous cell atrophy. Atrophy and atrophic changes can be . In starvation following depletion of glycogen and fat reserves. Mismothering is also quoted in starvation atrophy in neonates.Atrophy. laryngeal muscle atrophy occurs due to the injury to left recurrent laryngeal nerve and shoulder muscle atrophy (sweening) occurs due to suprascapular nerve injury. Chronic venous congestion results in centrilobular necrosis of liver due to inadequate oxygen and nutrition supplied to the hepatocytes. malabsorption. Pressure atrophy: In space occupying lesions like tumours.. Castration leads to atrophy of prostate. neoplasia etc. the neighboring tissues undergo atrophic changes mainly due to lack of nutrition from pressure ischemia. chronic infection. In fracture. abscesses etc. Pathogenesis  In atrophy. protein of the musculature and vital organs is lost. resulting in muscular wasting. chronic passive congestion. Endocrine atrophy: Prolonged steroid therapy leads to atrophy of zona fasciculata of the adrenal gland. In horses. o e. parasitism. That is excessive protein loss or degradation overproduction of proteins. anaemia) may lead to atrophic changes.

Organs may be fibrosed and become firm.    Pathological hyperplasia may be localized or generalized/diffused. epidermis or mucosal epithelium. cystic endometrial hyperplasia occurs in prolonged progesterone secretion. Microscopic changes  Cells are smaller than normal and decrease in number. These cells are primed from the matrix degradation products followed by proliferation under the influence of growth factors (HGF) and cytokines (TNF-α. Pathological hyperplasia may also lead to cancerous growth.e.The organ may become soft and flabby and loss of tone and tissue colour. Hepatic regeneration occurs following partial hepatectomy by the proliferation of surviving cells. renal fat etc. Sometimes brown atrophy is encountered.g.g. hyperplasia of connective tissue (e. prostatic hyperplasia in dogs and thyroid hyperplasia in case of goitre.e. indigested residual bodies in the cytoplasm HYPERPLASIA   Hyperplasia is the increase in the size of the tissue or an organ or a part of an organ due to quantitative increase in the number of cells. Compensatory hyperplasia: It occurs due to partial loss of hepatocytes in liver. fibroblast and blood vessels) occurs under the influence of growth factors. clear/yellowish gelatinous material is seen in place of fat especially cardiac fat. with reduction in the growth factors and adjuvants. Nodular hyperplasia in liver.) and aided by adjuvants like norepinephrine and growth inhibition influenced by TGF-β. Fat shows serous atrophy (indicating starvation) i. Sometimes. a cytosolic peptide and then it is destroyed (that is called proteasome).g.g. mitochondria and lysosomes and by ubiquitin-proteasome pathway wherein the proteins combine with ubiquitin.g. diffuse enlargement of an organ. Adipocytes become smaller. endometrial hyperplasia or effects of growth factors on target cells. papilloma virus infections. Brownish discolouration is due to the membrane bound. In canine uterus. spleen of aged dogs. e. . IL-6 etc. e. Pathological hyperplasia This is most commonly caused by excessive hormonal stimulation. Generalized/diffused hyperplasia.e. Compensatory hyperplasia can also be observed in abraded epidermis in which basal layer proliferates to form the superficial layers.e. Hyperplasia is classified into physiological hyperplasia and pathological hyperplasia Physiological hyperplasia   Physiological hyperplasia may be the result of hormonal influence as in the case of increase in the size of mammary gland due to glandular epithelial cell proliferation in puberty and pregnancy. complete disappearance of the cells is found. hyperplasia also occurs in viral infections involving the epithelium i. Interstitial hyaluronic acid and mucopolisacharides are increased. Localized hyperplasia . Morbid/ gross changes  Affected organs show decreased weight and volume.attributed to autophagocytosis with destruction of cytoplasmic organelles like ribosomes. wrinkling of surface membrane and tortuous blood vessels too large for the volume of the tissue. in wound healing.

The number and the size of the organelles will be increased due to the increase in the functional demand.g. smooth muscle 3. as it may lead to cancer. Hyperplastic ability depends on different adult cell types. Muscles in race and draft horses. it is considered as a double edged sword. e. It is also defined as the transformation of one cell type to another cell type within the embryological limits. transcriptional factor (C. cartilage. In metaplasia. Labile cells: These cells can proliferate normally. the compensatory mechanisms fail. one type of epithelium may be converted into another. the organ will be normal but the cells are bigger. in pregnancy with increased estrogen stimulation hypertrophy of uterus occurs and in lactation mammary gland development occurs under the influence of prolactin and estrogen.g.g. fibroblast growth factor). bone marrow cells 2. The hypertrophic changes are seen in the permanent/stable cells. Accordingly three cell populations are identified: 1. e. METAPLASIA AND DYSPLASIA METAPLASIA  Metaplasia is the reversible change in which one adult cell type is replaced by another adult cell type of the same germinal layer. Neurons. Permanent cells: These cells have lost their ability to regenerate/ become hyperplastic. e. Liver. smooth endoplasmic reticulum in hepatocytes are enlarged in chronic alcoholism and increase in the size of the rough endoplasmic reticulum and Golgi apparatus as a need for increased synthesis of proteins (e. Mechanism of hypertrophy involves many signal transduction pathways with induction of a number of genes and synthesis of cellular protein.g.fos) and vasoactive agents especially endothelin-1. e.g. Types of hypertrophy   Physiologic hypertrophy: It occurs following work or exercise/specific hormonal stimulus.g. Metaplasia may involve epithelial or mesenchymal tissue.With the continued haemodynamic overload. usually less special type or one type of mesenchymal tissue into another type. Compensatory hypertrophy: It occurs due to the loss of a part of the organ or loss of one of the paired organs (One kidney undergoes hypertrophy with the loss of the other) or due to the obstruction of the lumen in hollow muscular organ (Right ventricular hypertrophy in pulmonary stenosis). In microscopic view. Epidermis. its receptors (TGF-β. collagen and immunoglobulin). The number of the cells doesnot increase. bone. HYPERTROPHY   It is the increase in the size of the cells or the organ. Stable cells: These cells proliferate when need arises. cardiac and skeletal myocytes. e. So there will be increase in growth factors. resulting in the decompensation and cardiac failure. Mechanism . While metaplasia is reversible. Striated muscles are most commonly affected. the mitochondrial number varies with ATP requirements.

transitional epithelium of urinary bladder. The condition is mainly affecting the epithelium. carcinogens or other chemicals. Nutritional deficiency: Vitamin A deficiency produces squamous metaplasia of esophageal mucous glands of chicken. or ‗carcinoma in situ’. In dysplasia. nutritional deficiency. o Calculi: Calculi of salivary gland. . The developmental defect involved complex interactions among three germinal layers. pancreas etc. The condition is mild to moderate and reversed if the stimulus is removed.   Chronic irritation from chemicals. that induce chondro-osteogenic expressions. there will be loss of uniformity of cells and their architecture. o Smoking: In lung of smokers. o Estrogenism: Stratified squamous metaplasia of prostrate or urinary tract. The tissue specific and differentiation genes involved are bone morphogenetic protein. skin. The stem cells may differentiate following changes in signals through cytokines. Dysplastic changes are commonly found in the eye.Epithelial metaplasia Squamous metaplasia: . it is called ‗preinvasive carcinoma. TGF. biliary calculi. cuboid and columnar epithelial cells lining the eye and salivary gland ducts. Some transcription factors involved in the cellular differentiation are Myo-D for muscle.It may occur due to many reasons like chronic irritation. I. Dysplasia when marked and in which all layers of stratified squamous epithelium are involved. PPAR-γ for adipose tissue. nutritional deficiency etc. shape and orientation of tissue. brain and skeletal system. CBFA-1for osteoblast differentiation. neoplasm etc. growth factors and extracellular matrix. increased mitosis and disorderly arranged cells.  Metaplasia may arise from reprogramming of stem cells (Reserve cells in epithelium) or from undifferentiated mesenchymal cells present in the connective tissue.β etc. It is characterized by pleomorphism (Change in the size and shape of cells). DYSPLASIA    The term dysplasia is applied to the tissue malformed during maturation. abnormally enlarged hyperchromic nuclei. ciliated cuboidal and columnar epithelia of airways are converted into stratified squamous epithelium. There will be alteration in size. Metaplastic changes may be caused by chronic irritation. II Mesenchymal metaplasia  Osseous metaplasia in injured soft tissue and metaplastic changes in mesenchymal tissue results in the formation of cartilage and bone in mixed mammary tumour of dogs and myeloid metaplasia leading to extramedullary haematopoesis in adult liver and spleen following injury to bone marrow.

First four of them were described in first century (AD35) by the Italian scientist Cornelius Celsus.g. Rudolf Virchow (AD 858). toxins Repair produces scars that causes mechanical obstruction and loss of functions CARDINAL SIGNS OF INFLAMMATION   There are five important local signs of inflammation. toxins ) Cell injury (necrosis) Harmful Effects of Inflammation       Chronic inflammatory reactions e. the German pathologist added the fifth sign. Cardinal signs are mainly attributed to vascular changes at the site of inflammation. rheumatoid arthritis Atherosclerosis Pulmonary fibrosis Hypersensitivity reactions Insect bites drugs.    Reaction of blood vessels Accumulation of fluid & leucocytes in extra vascular tissues Inflammation and repair always go hand in hand Beneficial Effects of Inflammation   To destroy / dilute the injurious agent (microbes.INFLAMMATION Definition Reaction of vascularised living tissue to local injury caused by microbes or necrotic tissue. The cardinal signs are: .

Functio laeso) : The affected part looses its function due to swelling. Pain (L. Loss of function (L. adding volume to the tissue and exudates into the inflammatory area. Tumour): It is due to the increased blood flow. Heat (L. Chemical agents – acids. Swelling (L.Histamine − chemical mediators of inflammation Changes in the rate of flow  Increased vascular permeability (Vascular leakage) Leakage of plasma proteins ↓ ↓ Intravascular osmotic pressure ↓ ↑ Osmotic pressure of interstitial fluid ↓ ↑Outflow of fluid into interstitium . microbial virulence factors. etc) o Momentary vasoconstriction o Vasodilation (arteriolar dilatation – nerve stimuli from axonal reflex also) o Increased blood flow o Opening of new capillary beds o Brought about by substances . cold Immunological reactions – Ag – Ab reactions Nutritional imbalances – vitamins. minerals Necrotic tissue Vascular changes in acute inflammation Julius conheim(1839 – 1884)  Changes in blood vessels following injury (tissue damage. virus etc. Calor): It is due to the increased blood supply to area of inflammation carrying warm blood from the interior of the body and increased rate of metabolism at the site of inflammation leading to increased production of heat. electricity. Dolor): Pain in the area of inflammation is due to the increased pressure on sensory nerve endings and stretching of tissue due to accumulation of exudates. Rubor): It is due to the increased supply of blood (hyperemia) to the area of inflammation. radiation. pain and tissue destruction ACUTE INFLAMMATION AND VASCULAR CHANGES Aetiology (Causes) of inflammation       Infectious agents – bacteria. alkalies etc. fungi. Physical agents – burns.     Red (L.

o By increasing the capillary bed in the area o Swelling of endothelial cells o Hemoconcentration o Margination of leucocytes Slowing of blood flow – from capillary filing and endothelial swelling      Margination Rolling – selectin – selectin receptors Pavementing. Besides perivascular mast cells degranulate and release histamine which increase post capillary permeability. TGF-β) which are chemotactic to leucocytes and procoagulants for coagulation.integrin.as surface ligands increase → Leucocytes Adhesion.↓ Haemoconcentration Essential for movement of leucocytes into ECF    Haemoconcentration Endothelium becomes leaky Activated endothelial cells release ptostaglandin which causes vascular dilatation. Substance P is released by the nerve. heparin antagonizes coagulation and angiogenic and leukotrienes which induce pain. cytokines (IL-1. ICAM Emigration Diapedesis of erythrocytes  Movement of erythrocytes outside the blood vessel during iinflammation. Chemotaxis   Unidirectional migration of cells towards a chemical attractant It is the force that attracts leucocytes into the inflamed tissue Chemotactic agents Exogenous  Endogenous    Bacterial products Chemical mediators like C5a (complement) Leukotriene B4 Cytokines (interleukins) Phagocytosis  It is the process of taking particulate matter in the cytoplasm by cells Pinocytosis   Taking in fluid particles Discovered by ELLIE METCHNIKOFF in 1884 . TNF.

etc) from the liver and leucocytes and increased haematopoiesis in bone marrow and lymphopoiesis in lymph node and spleen. Proteases liberated induce tissue damage. hydroxyl radicals → H 2 O 2 CHEMICAL MEDIATRS OF INFLAMMATION I. Fever. basophils. 3. Engulfment o Regurgitation during feeding o During degranulation leakage of hydrolytic enzymes.Cellular  Preformed mediator in secretary granules Mediators Histamine Serotonin Source Mast cell. Kinins released cause vascular dilatation and nerve stimulation. Monocytes transform into macrophages to release collagenase. metabolic products ( H 2 O 2 ) and lysozymes from neutrophil into outside medium cause tissue damage. Recognition and Attachment o Micro-orgranisms are not recognized by neutrophils and macrophages until they are coated by naturally occurring serum proteins 2. IL-1 and TNF. Killing and Degradation o Brought about by reactive oxygen species like hydrogen peroxide( H 2 O 2 ) o Myeloperoxidase enzyme present in lysosome of neutrophils H 2 O 2 → HOCl (hypochlorous radical) ↓ Active antimicrobial (kills bacteria)  Myeloperoxidase deficient neutrophils o superoxide. elastases. Activation of systemic response leads to releaseb of acute phase proteins (complement. macrophages . platelets. platelets Platelets Lysosomal enzymes Neutrophils  Newly synthesised o Mediators Source  Prostaglandin All leukocytes. antimicrobial proteases. platelets aggregate and release PAF4 which is chemotactic to neutrophils and Coagulation factors causing polmerization of fibrin. complements. fibrinogen. PDGF stimulates fibrinogenesis andangiogenesis. Endothelial cell  Leukotrienes All leucocytes  Platelet activating factor All leucocytes. endothelial cell  Activated oxygen species All leucocytes  Nitric oxide Macrophages  Cytokines Lymphocytes.Steps in Phagocytosis 1. myalgia and endothelial cell activation.

Lysosomal components  Lysosomal components leak during phagocytosis or regurgitation. Lysozyme  Lysozyme (neuraminidase) is found in granulocytes. acid hydrolases and neutral proteases are responsible for vascular permeability. Large granules (azurophils) myeloperoxidases. histaminases and plasminogen activator. . C5a – Anaphylatoxins. Lysozyme catalyses the hydrolysis of peptidoglycans in bacterial cell wall. LTc4. The secondary mediators have similar or opposite effect. LTE4.It is present in mast cell and platelets of rodents. LTD4. leukotrienes are produced e. collagen. monocytes. bactericidal factor. C3b – phagocytosis of bacteria. tear and saliva. Liver – plasma   Factor XII (Hageman factor) activation – kinin system (Bradykinin).II. alkaline phosphatase. macrophages and produced by epithelial cells of mucosa and glands of intestinal tract and secreted in milk. Preformed mediators in secretary granules Histamine  Histamine is found in the granules of mast cells. Small granules contain lysosomes. C5b-9 – Membrane attack complex Biologic activity    Specific receptors on target cells Direct-enzymes Mediate oxidative damage Chemical mediators     Stimulate release and mediation of target cells themselves. When acted through platelets lipoxins which are potent chemoattractants are produced. Chemical mediators are short lived and scavenge oxygen species. Chemical action – one or many target cells with different effects. Serotonin  Serotonin (5-hydroxy tryptamine) . chemotaxis and tissue damage. basophils and platelets. Coagulation system Complement activation – C3a. Histamine and serotonin cause tissue damage. It increases the vascular permeability of venules and dilates arterioles and induces endothelial junctional gap early response to inflammation. It increases vascular permeability and involved in early inflammatory response. Arachidonic acid metabolites  The cell membrane phospholipids of neutrophils are acted upon by phospholipases.g. When arachidonic acid enters 5-lipoxygenase pathway.

Prostaglandin derivatives PGI2. Lipoxins) Note: Leukotrienes are 1000 times more potent than histamine Cytokines   These are derived from activated macrophages and lymphocytes and are proteins e. Leukotrienes. Platelet activating factor (PAF) . PGD2 cause vasodilatation while thromboxaneA2. IL-1 are produced by macrophages. Newly synthesised mediators Eicosanoids  These are derived from arachidonic acid from injures cell membrane phospholipids. LTE4 cause vasoconstriction. TNFα. LTD4.g. prostaglandins are produced. If acted by cyclooxgenase pathway. LTE4 are also responsible for increased vascular permeability. LTD4. These are prostaglandins and leukotrienes. LTD4 and HETE can induce chemotaxis and leucocytic adhesion ARACHIDONIC ACID METABOLITES (Prostaglandins. LTC4. PGE2. LTC4. γ-Interferon also induce acute phase response whereas interleukin 10 is a potent anti inflammatory cytokine.

Nitric oxide   Nitric oxide (NO) . endothelium). PAF causes increased vascular permeability and 100 to 10. eosinophils and basophils. Activation of Hageman factor results in cascade of reactions. hydrogen peroxide and hydroxide radicals) derived from membrane damage like neutrophils can cause tissue injury and endothelial damage. Acute phase proteins . beta chemokines (C-C) attract monocytes. clotting system and fibrinolytic system. neutrophils.  It is derived from degeneration of membrane phospholipids (platelets. an alpha 2 glycoprotein on fibroblast surface and basement membrane. PLASMA PROTEIN SYSTEM Plasma proteases (Kinin.000 times more potent than histamine higher concentration of platelet activating factor can stimulate platelets. The fragment which enhances inflammatory process and this stimulates complement system. Hence of diagnostic value in inflammation. lymphocytes. foreign material and soluble protein. TNF alpha) Exmples function of acute phase protein     Fibrinogen. alpha chemokines (C-H-C).Microbicidal agent in activated macrophages causes vascular dilatation. It is considered as first host defence against viral infection. These are synthesized in liver in response to cytokines released by inflammation leucocytes (IL-1.attract neutrophils. kinin system. fibrin Coagulation forming coagulant polymers C3 Backbone of complement cascade responsible for destruction of bacteria C-reactive protein Initiating complement dependent opsonisation Haptoglobulin Antioxidant by binding haemoglobin and saving iron Interferons  Interferons are produced by host cells in response to stimulation by virus. It is soluble and short lived free radical gas. Chemokines   Chemokines are responsible for activation and migration of leucocytes in acute inflammation. Fibronectin. intracellular bacteria. IL-2 and TNF can produce endothelial activation adhesion of leucocytes production of arachidonic acid metabolite and nitric oxide. gamma chemokines (C) attracts lymphocytes and CX3C causes attraction and adhesion of monocytes and T-cells. when in plasma helps in opsonisation of bacteria and promotes phagocytosis. enhance leucocyte adhesion to endothelium and stimulate vasoconstriction.They are not normally present in plasma but markedly increase after injury. Fibrinolytic systems) . Clothing. Oxygen derived free radicals  Oxygen derived free radicals (superoxide.

The kinins are potent mediator of vasodilatation. Complement system  Complement represented as C consists of 20 proteins in an inactive form in plasma and body fluids. Complement is mainly synthesised by liver. C3b is a major opsonin protein which adhere to bacteria (opsonisation). pain and smooth muscle contraction. But both the pathways converge to produce a membrane attack complex (MAC) which is responsible for lysis of bacterial cell membrane and also results in mediating inflammation. classic or alternate pathway. phagocytosed and destroyed by neutrophils and monocytes. Kinin system  The vasoactive polypeptide (kinins) are derived from kininogen (plasma globulins). The prekallikrein is converted to kallikrein which will be converted to bradykinin that induces vascular permeability. histamine release from mast cells (C3a) and procoagulant from platelets. vascular permeability and vascular dilatation Activated Hageman factor is also involved in conversion of prothrombin to thrombin which in turn aids in conversion of fibrinogrn to fibrin. It is recognised. e. The .g. pain. Kallikrein also mediates plasminogen. The fibrinolytic peptides and split products of fibrin can induces vascular permeability and chemotaxis. increased capillary permeability. Complement system may be activated in one of the two ways. basement membrane and platelets to produce prekallikrein. clotting and fibrinolytic system    The Hageman factor (factor XII) is activated on contact with collagen. chemotaxis.Kinin.

d4. Actions of mediators in acute inflammation Action Vasodilation Mediators Histamine Prostaglandins Nitric oxide Vascular permeability Vasoactive amines C3a and C5a Bradykinin Leukotrienes C4.bradykinin induces vascular leakage from post capillary venules. It is 10 times more active than histamine but short lived. Clotting system  Coagulation is seen following damage of endothelium in inflammation through fibrinolytic system the initiated by activated Hageman factor. E4 Platelet activating factor Substance P Leukocyte chemotaxis and activation C5a Leukotriene B4 Chemokines TNF and IL-1 Fever TNF and IL-1 Prostaglandins Pain Prostaglandins Bradykinin .

Silica particles Causes of chronic inflammation     Bacteria – Pasteurella aviseptica. dust. nodules (granuloma) kidney – pitted appearance Smooth.g. calluses Gross appearance    Gray and firm. Erysipelothrix rhusiopathiae Phytotoxins – Crotalaria.Shrunken Multiple nodules Vascular and cellular response is less Proliferation of fibrous connective tissue New blood vessel formation Mononuclear cells ─ predominant .Corrugated intestine Microscopical appearance     Chronic inflammation .Liver .CHRONIC INFLAMMATION      Infiltration with mononuclear cells Tissue destruction and repair New blood vessels & fibrosis Long duration o Follow acute inflammation – persistence of causative agent o Chronic from the beginning – irritants of low intensity o Example – Tuberculosis . watery (newly formed) Yellowish. tough. dense. Johne‘s disease o Fungal diseases Prolonged exposure to toxic agents o Example – Asbestos. soft & easily cut Chronic inflammation . white.JD . senecio Foreign bodies – sharp objects. worms.: kennel granuloma. hard (mature variety). inert objects Constant & repeated mechanical irritation o e.

monocytes are attracted to the site that are not ineffective in phagocytosis. These are mostly caused by bacteria and fungi predisposed with deficient immunocompetency. asbestos) which cannot be killed or fully digested. Chronic active inflammation includes apart from neutrophils. metritis and epididymitis (Brucellosis). lymphocytes and plasma cells Formation of new blood vessels and fibrosis Longer duration Two types of chronic inflammation   This may be sequel of persistent and resolved acute inflammation It may develop as a slowly evolving chronic process without an acute inflammatory phase Persistent acute inflammation   The lesions of persistent inflammation are progressively dominated by the presence of macrophages. fibrous tissue and blood vessels e. So that the cells continue to infiltrate the lesion and are found in large numbers.g. Evolving chronic inflammation  Diseases like tuberculosis. debris from an injured tissue. Macrophages Plasma cells Lymphocytes Giant cells Neutrophils — in bacterial infection Encapsulation o o o o o Chronic inflammation is characterized by     Tissue destruction and repair Infiltration of macrophages. fungi. Granulomatous inflammation   This is a form of chronic inflammatory process in which aggregates of large highly activated macrophages are present. aberrant parasite (Toxocara larva) or inert substances (silica. Acute fibrinous pericarditis . When the macrophages take up bacteria. It lacks cardinal signs of acute inflammation. The granulomatous lesions develop slowly over a period of several weeks or months before producing clinical signs of disease. The microorganisms involved do not cause endothelial damage and are not chemoattractive. presence of macrophages and plasma cells which may be associated with osteomyelitis. actinobacillosis and osteoarthritis in which chronic inflammation begins as an asymptomatic process in which neutrophils are not present but infiltrated with macrophages which deals with persistent injury. Other ways of classification of chronic inflammation . So this foamy macrophages are referred to as an epithelioid cells which are the hall mark of granulomatous inflammation. The macrophages become larger and foamy because of accumulation of causative agents. so that acute inflammatory signs and neutrophils are not seen.infiltrated with fibroblasts and collagen if not resolved.

also epithelioid macrophages. fibrin and plasma protein of acute inflammatory response. e. the centre is having grey-white. Usually it can be noncaseating or caseating.g. giant cells and lesser number of lymphocytes and plasma cells. lymphocyte and plasma cells. replace or obliterate the tissue) Impairs mobility Epithelial surface – hyperplasia – Metaplasia – Neoplasia Increase intracranial pressure . peripheral zone of fibroblast.g.This type of inflammation contains similar cellular exudates like granulomatous inflammation that multifocal infiltration of neutrophils. variable epithelioid macrophages.destruction neurons and glia Differences between acute and chronic inflammation Acute Short duration Irritant – Sever Long duration Low intensity Chronic Marked vascular Changes Less prominent Profuse exudate Soft in consistency No fibrosis Scanty Hard in consistency Proliferation of fibro vascular connective Tissue and epithelium Granulomatous inflammation    Chronic inflammation Circumscribed lesion No exudates or cellular changes The histiocytes (macrophages) in the lesion have large amount of cytoplasm and resemble epithelial cells called ―EPITHELOID CELLS‖ . Sometimes both lymphocytes and macrophages may predominate (lympho-histiocytic) seen in early stages of chronic inflammation like viral infection. yellow pasty necrotic debris resembling cheese (Latin caseous = cheese) e.Basic cellular exudate . fibrin and plasma proteins. it also contains neutrophils. In caseating granuloma. deep seated mycoses. Mycobacteria and protozoa Pyogranulomatous inflammation .g.Predominantly activated macrophages. Non-caseating granulomas are round to oval containing numerous macrophages. Epitheloid cells fuse to form ―Giant Cells‖ Foreign body giant cell .     Chronic inflammation – Simple type. Granulomatous inflammation . A nodule like granulomatous areas with neutrophils is termed as pyogranuloma e. some multinucleated giant cells. Granuloma .g.e. Brucella. bacterial infection with Nocardia. Langhan‘s cell . Common in blastomycosis. tuberculosis Result of chronic inflammation       Delayed healing Permanent change or scar formation Distortion / Disfigurement of the organ / tissue ( Inflammatory cells displace. Chronic active inflammation .Besides cellular components of chronic inflammation.Distinct type with well defined macrophage infiltration. predominantly cellular exudates predominantly containing lymphocytes. Macrophages and plasma cells are fewer.

TB. Actinobacillus Fungus – Aspergillus fumigatus Foreign bodies – Silica.Causes for granulomatous inflammation    Bacteria – TB. Actinomyces. rabies Intranuclear − i/n − infectious canine hepatitis i/c and i/n − Small pox. asbestos. ↑ eosinophils / macrophages ↓ 72hours − Hot. Canine distemper . inert material Result   Helps in localising the infection Allows inflammatory and immune mechanism to act for longer periods of time Allergic inflammation   Animal / person previously sensitized to foreign bodies Diagnosis of JD. JD. painful diffuse swelling ↓ Subsides Viral inflmmation          Obligatory parasites Cannot survive outside the cells Once inside the cell. protected against antibodies ―INCLUSION BODIES‖ − aggregates of virus Basophilic − replication is complete Acidophilic − ongoing replication Intracytoplasmic – i/c – Fowl pox. Glanders Sensitized animal ↓ Injection of protein (Antigen) ↓ 24hours − Neutrophils / oedema ↓ 48hours − Number of neutrophils . vaccinia.↓ neutrophils.

Rabies – Cytocidal Inflammatory cells . Ehrlichia canis. o Microphages of Metchnikoff o Polymorpho nuclear cells o First line of cellular defense o Pus cells Morphology / Character o 10 – 20 µ diameter o Band shaped or segmented nucleus (3-5 segments) (PMN) o Cytoplasm eosinophilic o Granules in cytoplasm rich in lysosomal enzymes o Rapid amoeboid movement . Plasma cells. Chlamydia psittaci (intermediate between bacteria & virus) Obligatory parasites Transmitted through arthropod vectors CELLS IN INFLAMMATORY RESPONSE Neutrophils   Synonyms etc.g Vaccinia Necrosis alone – FMD.Reactions of cells to virus   Hyperplasia − Shope Papilloma virus Hyperplasia and necrosis − Fowl pox Hyperplasia ↓ ↑ Keratinisation ↓ vacuolation of cytoplasm ↓ inclusion bodies ↓ Necrosis    Proliferation quickly followed by necrosis. Macrophages o No neutrophils o No suppuration Rickettsial inflammation    Anaplasma marginale. e.Lymphocytes.

o  Origin o o o Aggressive phagocytosis   Myeloid tissue of bone marrow Attracted to injured area by chemotaxis (C3. e.C5) No reproduction at inflammatory site Condition encountered o First line of defense o Pygoenic organisms o Increased in early inflammatory response Functions o Phagocytosis o Killing and destruction of bacteria and dead cells through liposomes and proteolytic enzymes o Energy source for other cells (MNC) Eosinopihls  Morphology / Character o o o o Cytoplasmic granules are large and eosinophilic and contain basic protein (toxic to parasite) Motile.g. histamine and proteolytic enzymes o Some animals rich in serotonin . chemotactic Nuclues . asthma in man. sluggishly phagocytic.Bilobed  Origin Myeloid tissue of bone marrow No reproduction at site of inflammation Condition o Appear late in inflammation o Most prominent in conditions where there is no immune response. hay fever. parasitic conditions) o Allergy o Parasitic infections Functions o Chemotactic o Phagocytic – killing parasite o Hypersensitivity reactions o o   Basophils   Morphology /Character o 10 – 15 µ in diameter o Blue granules in cytoplasm o Motile o Non-phagocytic o Seen in small numbers in inflammation o Large lobulated nuclei o Granules contain heparin and histamine but no acid hydrolyses Mast cells o Connective tissue cells o Mononuclear nuclei o Larger in size o Abundant cytoplasm o Granules contain heparin.

anaphylaxis (C3a and C5a anaphlyotoxins) o In acute inflammation  Trauma  UV light  Heat  Cold Lymphocytes   Morphology / characters o 7 – 12 µ in diameter o Nucleus round o Heavy chromatic compact granules within the nucleus o Cytoplasm invisible o Cytoplasm.g. homogenous. pale blue and may contain a few azurophil granules Origin   Two lymphocytic population . Functions o Both basophils and mast cells release heparin / histamine in response to Ag – Ab complexes o The immunoglobulin IgE binds relectively to the surface of mast cells and basophils ↓ Triggers degranulation ↓ Release of histamine and other mediators. eccentric Cart wheel like arrangement of nuclear clnomatin . glucocorticoids o Have and inflammatory response Functions o Humoral and cell mediated immunity o o o Plasma cells    12 – 15 µ Nucleus similar to lymphocytes.T lymphocytes → Cell mediated immunity B lymphocytes transform into PLASMA CELLS. When they come in contact with antigen and produce antibodies – Humoral immunity Condition o Occurs late in inflammation 48 – 72hours o Viral infections particulary in CNS o Brain & Spinal cord → Perivascular cuffing o Endocrine secretions from pituitary and adrenal cortex control the number of lymphocytes e.

fibronectin.  Cytoplasm abundant Slightly amoeboid and phagocytic Origin  From lymphocytes Function  Antibody production.Spleen / lymphnode Skin Bone Langhan‘s cell Osteoclasts Macrophages + Monocytes . endotoxin.Mononuclear phagocyto system   Condition encountered o Arise 48 – 72 hours in inflammation o Late o Response to immune mediated reaction. Activated T cells secretes gamma interferons which activates macrophages Function o Phagocytosis o Second line of cellular defense o Chemotactic o Produce potent enzymes that degrade connective tissue . chemical mediators. Macrophages     Synonyms o Macrophages of Metchnikoff o Second line of cellular defense Morphology/ Character o 12 – 20 µ in diameter o Nucleus round to oral o 1 – 2 nucleoli o Macrophages may bunch together to form epithelioid cells o Amoeboid & phagocytic Origin o Macrophages originate from monocytes o Monocytes emigrate from the blood into the inflammatory lesions and transform into macrophages o Capable of reproduction at the site of inflammation Monocytic phagocytic system Histiocytes Kupffer cells Microglial cells Alveolar macrophages - Connective tissue Liver Nercous system Lung Fixed / free macrophages .

endogenous pyrogens) Release factors in wound healing Secrete lysosymes. MYCOSES Tumor . Mechanism . respiration and heart rate. It is a syndrome of elevated body temperature increased due to that effect of potent cytokines released by inflammatory cells.giant cell  Nuclear division without cytoplasmic division Reed . Langhan‘s giant cell → TB. Definition   Fever is a complex systemic response that includes increased body temperature.g.Sternberg cells  Hodgkin‘s disease (mirror image nuclei – two) Touton giant cell Xanthomas 10 – 15 µ diameter SYSTEMIC EFFECTS OF INFLAMMATION    Fever Suppression of fever Leukocytic response Fever  Fever is the main response in acute inflammation.o o o o Release substances responsible for fever & leucocytosis (prostaglandins. interferon defense mechanism Serves to process antigens in CMI Giant cells  Multinucleated cells formed by fusion of macrophages Foreign body giant cell  Fusion of macrophages evoked in response to foreign body 50 – 100 nuclei   Nuclei arranged in periphery of cells (horse-shoe pattern) e. JD.

Bacterial products. toxins. immune complexes. Clinical effects in mammals     Anorexia somnolescence malaise shivering and search for warmth (chills) . decreased appetite Increased acute phase proteins Haemodynamic effects (shock) Neutrophilia 2. IL-8. physical injury. other cytokines Macrophage (and other cell) activation IL-1 / TNF 1. Leukocyte effects  Increased cytokine secretion (IL-1. The most important thermoregulatory mechanism is a redirection of blood flow to skin to deep capillary bed i. pulse rate and decreased sweating.IL-6. Endothelial effects      Increased leucocyte adhesion Increased PGI synthesis Increased procoagulant activity Decreased anticoagulant activity Increased IL-1.e. Acute phase reactions     Fever – increased sleep. PDGF 3. intended to decrease heat loss from body surface. Endocrine changes: Increased level of glucocorticoids. Fibroblast effects    Increased proliferation Increased collagen synthesis. increased PGE synthesis 4. growth hormone and aldosterone and decreased vasopressin and Autonomic changes: Increased blood pressure.    The endogenous pyrogens of leucocytic origin elevate hypothalamic thermostat. increased collagenase Increased protease. IL-6) The progression of fever depends upon    release of pyrogen from leucocytes suppression of body heat loss by cutaneous vasoconstriction increased heat production and shivering The following changes occur in fever    Metabolic changes: Secretion of acute phase proteins.

Causes Causes of fever includes         Bacteria (endotoxin .antibody complexes) . Major acute phase proteins are Creactive protein (CRP) and serum amyloid protein (SAP) .lipopolysaccharide of gram negative bacteria (multiple causes)) Viruses Protozoa Fungi Rickettsia Hypersensitivity reaction (antigen .severe crushing. major surgery Vascular disorders . Accelerated distribution of leucocytes Increased phagocytosis Efficient killing of organisms Quick formation of antibodies Higher temperature: Bacteriostatic The acute phase reactions are mediated by interleukin-(IL-1) and tumour necrosis factor (TNF) which induce secretion of acute phase proteins by hepatocytes.infarction Neoplasm The benefits of fever includes       Increased neutrophils production.stimulate pyrogen release Mechanical injury .

Cell cycle checkpoints  Cell cycle checkpoints are used by the cell to monitor and regulate the progress of the cell cycle.g. The dividing cells undergo cyclical change i. The cyclins synthesized during specific phase of cell cycle are involved in activating cyclin dependant kinases (CDK). The members acting on cyclin D/CDK4 and cyclin D/CDK6 are p15. The time taken by different phases is as follows Phases Time taken (hours) G1 S G2 M         5 7 3 1 The cell is usually in interphase and G1 is most variable period. Cyclin D gene sare overexprssed in many cancers so that neoplastic transformation occurs. CYCLINS. p18 and p19. Cell cycle is also regulated by CDK inhibitors. the cyclins leave their activity.e cell cycle and it has four phases. The cell cannot proceed to the next phase until checkpoint requirements have been met. p27 and p57. A premitotic growth phase or G2 phase Mitotic phase or M phase o A cell takes16 hours to give rise to another cell. G2 to M phase transistion is regulated by cyclin B/CDK1. This is the way the cell cycle or proliferation is regulated. cyclin A/CDK1. cyclin D/CDK6.     Presynthetic growth phase or G1 phase – this is thetime gap between end of mitosis and start of DNA synthesis. Once the job is completed. CDKNIA (p21). An alternative model of the cell cycle response to DNA damage has also been proposed. allowing verification of necessary phase processes and repair of DNA damage. p53 plays an important role in triggering the control mechanisms at both G1/S and G2/M checkpoints. G1 to S phase is regulated by cyclin D/CDK4. breast cancer. GROWTH FACTORS . known as the post replication checkpoint. Two main checkpoints are: the G1/S checkpoint and the G2/M checkpoint.CELL CYCLE. G1/S transition is a rate-limiting step in the cell cycle and is also known as restriction point. e. S phase is regulated by cyclin D/CDK2. Synthetic phase or S phase – this is period of DNA synthesis and beginning of mitosis. e. cyclin D/CDK2. Checkpoints prevent cell at specific points.hepatic tumour. CDKN2A (p16). The checkpoints are designed to ensure that damaged or incomplete DNA is not passed on to daughter cells. G0 state wherein cell proliferation is arrested.g. GROWTH FACTORS AND HEALING CELL CYCLE AND CYCLINS Proliferationof cells are important in degeneration and repair and also a feature in neoplasia.

epidermis. PDGF is responsible for migration and proliferation of fibroblasts. epithelial cells. endothelial cells Permanent cells   Non–dividing cells Neurons. These are involved in angiogenesis. development and haematopoesis. Fibroblast growth factor (FGF): It includes acidic and basic FGFs. cell migration and proliferation of endothelial cells. TNF-α is also angiogenic in nature. they are involved in wound repair. macrophages and smooth muscle cells. It is also inhibitory to most epithelial cells‘ growth. GFs play a role in the movement of inflammatory cells. PDGF may be released upon activation of platelets. Besides. differentiation and in wound healing. also plays a role in angiogenesis of chronic inflammation and healing of wounds. kidney pancreas. macrophages. muscle cells (cardiac. T cells and macrophages.It induces fibrosis by stimulating fibroblast chemotaxis. . Specifically. lymphatic endothelial cell proliferation induced by VEGF. endothelium. paracrine. Both are mitogenic for epithelial cells and fibroblasts.g. Transforming growth factor-alpha (TGF-α) is homologous to this factor. Tumour necrosis factor-alpha (TNF-α) and Interleukin-1 (IL-1) : These cytokines play a role in fibroplasia by attracting fibroblasts and increasing collagen synthesis. Vascular endothelial growth factor (VEGF): It promotes formation of blood vessels (Angiogenesis). collagen and fibronectin synthesis and inhibition of collagen degradation. Therefore.Continuously dividing cells. Transforming growth factor-beta (TGF-β): It is derived from platelets. healing occurs by 1. bone marrow cells Stable cells    Quiescent cells Undergoes division occasionally Liver. a progression factor which acts by combining with EGF receptors in the cell membrane. It is a complement factor and requires a progression factor for its activation. Platelet derived growth factor (PDGF): It is stored in platelets and of 30-kDa size. Healing by substitution Depending on the proliferation potential of the cellsas described above. These are polypeptides found in the serum and/or elaborated by cells. endothelium and tumour cells. HEALING (TISSUE REPAIR) Tissue .Growth factors (GF) act by autocrine. in contractility of cells. Healing by regeneration 2. PGDF is important in angiogenesis.Proliferating potential of cell types Labile cells . fibroblasts. endocrine or signalling pathways. Basic FGFs are found in many organs and released by activated macrophages. skeletal) Hence. Acidic FGF is usually found in neural tissue. The main growth factors are:       Epidermal growth factor (EGF): It is a polypeptide of 6-kDa. e.

Namely.g. protein synthesis Remodelling of connective tissue Healing by primary union or first intention   This type of healing occurs in clean surgical approximated incision ie. infarction. Type III collagen is deposited ea sue and is replaced by adult type I collagen which accounts for wound strength. surface wound with large defects. It is a complex but orderly phenomenon involving a number of processes. collagen and proteoglycan rich ground substance. abscesses.. fibroblasts. the defect is marked by depression and decrease from its original size. granular appearance of wound surfaces) grows in from the margin to fill the defect but at the same time the wound contracts i.e.      Acute inflammatory reaction following initial injury Parenchymatous cellular regeneration Migration and production of parenchymatous and connective tissue cell Extracellular matrix. Collagen is arranged vertically cised space is filled with granulation tissue. The wound is filled with tissue debris. Microscopically granulation tissue consists of new capillaries. Newly formed blood vessels disap ar tissue consists of granulation tissue which is devoid of inflammation covering intact epidermis. ulceration. a few erythrocytes and bacteria. Abundant granulation tissue (soft. Granulation tissue begins to appear.Wound healing Wound healing is not a separate process and occurs along with the inflammatory reaction. Collagen fibre begin to appear and epi oliferation is maximal oliferation of fibroblast with continuous collagen accumulation producing a scar. Initially granulation tissue is soft and spongy due to leaky blood vessels. pink. The sequence of events occurring in primary union is given below ot filling the incised area eutrophilic infiltration sal cell proliferation and epithelial closure takes place by 24-48 hours acrophages replace neutrophils. Neovascularisation is maximal. Healing by second intention  The wound involved shows extensive loss of cells and tissue. e. Injury – open wound – excess loss of tissue – infected – necrosis – inflammation ↓ Blood clot ↓ . limited bleeding and tissue destruction.

capillaries grow vertically and project towards the surface. sebaceous gland. hair and hair follicles and pigment. Fibroblast also proliferate to fill the gap ↓ There is a definite order. Fibroblast grows perpendicular to capillary and parallel to surface – pulling pressure of the wound ↓ Surface – fibroblasts are arranged parallel to capillaries exerting tension towards wound surface for easy closure.24 hours – neutrophils infiltrate to destroy irritant ↓ 48-72 hours – macrophages and lymphocytes infiltrate ↓ Removal of necrotic and cellular debris by liquefaction by macrophages ↓ Red granules from underneath (granulation tissue) represent proliferating capillaries. the scar appears dry and unpigmented white and puckered as it becomes avascular and shrinkage of collagen . So. This arrangement differentiates granulation tissue from fibrosarcoma which lacks orderly arrangement ↓ The surface is closed by the epithelium proliferating from the margin ↓ The tissue is devoid of sweat gland. Base .

This condition is called proud flesh or excess granulation tissue. Reason for its development is not known. This condition may recur after the removal. it is essential for remodelling of extracellular matrix Metabolic factors o Diabetes mellitus – delays healing o Hyperadrenocortism Circulatory stasis or adequacy of blood supply o Inadequate blood supply – delays healing Hormones – concurrent glucocorticoid therapy hinders inflammatory and reparatory process Local factors    Infection can delay healing Mechanical – movements directly affect wound healing Foreign bodies impede healing .Septic wound . Keloid  Keloid is another condition.Healing by substitution Exuberant granulation or proud flesh  Sometimes the granulation continues to grow in abnormally large amount due to irritant. This is found in horses and black people having some genetic or familial predisposition. movement or trauma which prevents healing. The connective tissue below the epithelial covering continues to proliferate. Systemic and local factors influencing wound healing Systemic factors     Nutritional o Vitamins – vitamin C is required for collagen synthesis o Proteins deficiency – starvation o Sulphur containing amino acids (methionine and cystine) are important and required for intermediate forms of collagen o Zinc – as metalloenzyme.

There is breakage of tolerance to the self-proteins.  Size. thyroid shows interstitial lymphoplasmacytic infiltration with germinal centres. Erythrocytolysis occurs following antigen-antibody attachment to the surface membrane of erythtocytes or by removal of such cells by the splenic macrophages. There is involvement of T lymphocytes. Autoimmune thyroiditis Causes    Genetic predisposition (Doberman dogs) Autoantibodies Lymphocyte mediated mechanisms Pathogenesis    Exact mechanism is not known. clonal deletion). Microscopically. regenerative anaemia with high reticulocyte counts. causing hypothyroidism. hyperlipidosis and pyoderma in dogs. Two major autoimmune diseases are thyroiditis and haemolytic anemia. . location and type of wound Cold inhibits wound healing Others     Old age-Healing is slower than young ones. The tolerance of CD4+ TH cells is critical in preventing autoimmunity. Chemotherapeutic agents Radiation Immunodeficiency AUTOIMMUNE DISEASES Definition The animal reacts to its own tissue (endogenous antigen) to incite production of antibodies or sensitized lymphocytes. Other conditions are rare in animals. alopecia.   Autoimmune diseases are prevented by elimination of sensitized T and B lymphocytes by the process of apoptosis in the thymus and bone marrow during development (Central tolerance. There will be low haemoglobin with spherocytosis and direct Coombs test (antiglobulin) is positive. The thyroid follicular epithelial cells are destroyed by T cells in dogs. Signs: Obesity. Autoimmune haemolytic anaemia  The disease is characterized by severe haemolytic anaemia and thrombocytopenia. lethargy. in the peripheral tissues (Peripheral tolerance) and clonal anergy (Clonal avoidance) by defective presentation of cells.

capillary stasis. resulting in paralysis of tail and urinary and anal sphincters. The bullae form under the stratum corneum progressing to scabs and alopecia. Microscopically. proteinuria and polyarthritis are seen. Idiopathic polyradiculoneuritis  It is a group of diseases of inflammation of peripheral nerves. Grossly. The variant of pemphigus is known as pemphigus foliaceous in which painful skin disease develops in the face and ears. characterized by mononuclear cell infiltration. progressed to tetraparesis. Neuritis of the cauda equine  Neuritis of the cauda equine (Guillain-Barre syndrome-idiopathic polyneuritis. a postinfectious paralytic disease that typically follows Influenza infection) in which segmental demyelimation is seen in spinal nerve roots of horses. Systemic autoimmune diseases  Canine lupus erythematosus: A rare disease in which progressive haemolytic anaemia. nerve roots and ganglia. Renal failure causes death due to glomerulonephritis and plasma cell infiltrations. Bearded collies. antiglycocalyx antibodies are produced against keratinocytes which affect basement membrane of epithelium. Pemphigus     It is characterized by bullae formation in the skin and mucous membrane of dogs and humans. lesion is seen in the nose.   Cryopathic autoimmune haemolytic anaemia (Cold haemagglutinin disease in dogs and horses): The dog is anaemic. agglutination and lysis of erythrocytes are seen. Anaemia is observed only when the animal is having IgM auto-antibodies or exposed to cold. Lymphocytic infiltration in synaptic clefts occurs at a later stage interfering with release of acetylcholine and diminishing the total area of postsynaptic contents. ears and extremities in dogs. Footpad lesions are common e. Myasthenia gravis   The autoantibodies bind to acetylcholine receptors at motor endplates resulting in progressive muscular weakness and low exercise tolerance. The animals are alert and show initial signs of weakness to flaccid symmetric quadriplegia and may be segmental demyelination with perivenular lymphoid infiltration in the ventral nerve roots of spinal cord and some peripheral nerves. Oral mucosa is affected in dogs with loss of epithelial cell coherence and acantholysis.g. . thrombocytopenic purpura. Disintegration of myelin and infiltration of mononuclear phagocytes and macrophages into the sacral intradural rootlets. In autoimmune pemphigoid. Autoantibodies are produced against epithelial cell glycopoteins. Congenital disease occurs in Jack Russell and smooth fox terrier dogs. axonal degeneration and axonal reactions in lower motor nerves Idiopathic polyneuritis in dogs (Coonhound paralysis)  There is ascending symmetrical paralysis beginning 7-14 days after scratches or bites of raccoons.

translucent amyloid substance is deposited between capillary endothelium and adjacent cells. The preamyloid substances are soluble and synthesised in the cytoplasm and deposited in the extracellular spaces.5 to 10 nm in diameter. Under polarized light. The abnormal variant proteins are continuously incorporated to form fibrils.STARCH) means starch-like. Amyloid light-chain (AL): It is produced in plasmacytoma and the precursor is immunoglobulin light-chain. Amyloid is a pathologic glycoprotein deposited in the extracellular spaces and forms fibrils on polymerization. β-pleated sheet configuration is seen in X-ray diffraction. The AI occurs in pulmonary arteries and derived from apolipoprotein AI. Pathogenesis      The main event occurring in amyloidosis is the deposition of amyloid fibrils due to abnormality of protein processing. The P-component which is a glycosa-amino-glycan (GAG) facilitates polymerization of amyloid. Types/Sources of amyloid     Amyloid associated (AA): It occurs in chronic diseases and septic conditions. Lymphocytic infiltration is seen around the dermal blood vessels of dogs. In the brain of aged animals. Amyl(o) . but not in the kidneys. Platelet destruction (autoantibodies to platelets) leading to thrombocytopenic purpura is manifested as haematuria. The anaemia is acute with severe haemolysis and positive antiglobulin (Coombs) test. This makes the fibril resistant to digestion by macrophages and phagocytic cells and hence accumulates in tissues. The amyloid is resistant to enzymatic digestion and progressively accumulate in tissues until the underlying disease process persists. Amylon. green birefringence is noticed because of alignment of fibrils. Precursor is serum amyloid associated protein (SAA). beta amyloid protein is produced from beta Amyloidosis  It is an immunological disorder in which homogeneous. The sources of amyloid may be acute phase proteins. epistaxis. non-branching hollow-cored tubules of unknown length. AMYLOIDOSIS Amyloid (G. The amyloid forms a β-pleated sheet despite their chemical heterogeneity. Amyloid fibrils are 7. . Splenic active macrophages remove the amyloid fibrils. The fibrils may disappear following the removal of cause. IAPP is associated with pancreatic islets and derived from islet amyloid polypeptide. rigid. Histological characteristics   Amyloid is specially stained with Congo Red. petechiae and ecchymoses in the skin and mucous membrane. The GAG makes the amyloid to stain with iodine. immunoglobulins and endocrine secretes.  Thymus shows medullary lymphoid follicular development.

deposited around the blood vessels is more dangerous. neo-new. The soluble immunoglobulin becomes insoluble with defective degradation. The amyloid is deposited around the central artery of splenic follicles and it forms sheet like deposits which is referred asbacon spleen and it may protrude resembling like a grain of sago known as sago spleen. Secondary amyloidosis     The condition may be associated with chronic diseases like tuberculosis. repeated exposure to antigens as in antisera and antitoxin production in horses and B cell dyscrasia (plasmacytoma) in humans in which immunoglobin light chain deposition occurs. The condition is not associated with any diseases e. amyloid deposition occurs between capillary endothelium and epithelium of glomeruli interfering with glomerular filtration. The amyloid. the organ is swollen. In renal amyloidosis. lymph node and adrenals are commonly affected. the amyloid deposition may be diffuse or focal. amyloid deposition and fall in the SAAs level are found. kidney. gray and translucent. doughy in consistency. Splenic corpuscles become large.g. horses and chickens. liver. plasia. The deposition of amyloid is found between the endothelium of sinusoids and cords of hepatic cells. In the initial preamyloid phase. pale and yellow to orange in colour Effects of amyloidosis   Hypovolumic or haemorrhagic shock may occur following hepatic rupture. there is accumulation of reticular cells and macrophages in the spleen and other lymphoid tissue with consequent rise in plasma SAAs and globulins. Animals affected are dogs. The enlargement and ischaemic anoxia leads to tubular epithelial degeneration and necrosis. mottled. septic conditions and neoplasia.development or formation) . pits on pressure and ruptures easily because of its friable nature. The serum amyloid associated proteins increase (SAA) and converted to insoluble amyloid associated substances. uremia and death In pancreatic amyloidosis. NEOPLASM Neoplasm (G. Grossly. Blindness may be encountered in horses in with conjuctival amyloid deposition. nephrotic syndrome.6 from macrophages stimulate the liver to synthesize SAAs. degeneration and necrosis of cells will occur amyloid precursor protein. Types of amyloidosis   Primary amyloidosis Secondary amyloidosis Primary amyloidosis   It results from antigen-antibody reaction and deposition of its precipitates. This occurs in two phases. supply of nutritents and removal of waste products and stenotic vessels. known as amyloid phase. marked proteinuria. Spleen. interleukin-1and interleukin . The organ is waxy in consistency and the cut surface is grayish. Probably. Hepatocellular atrophy occurs from pressure and nutritional deficiency. Due to interference with gaseous exchange. cattle. During the second phase. Liver is enlarged with rounded edges. the cytokines. Pressure atrophy of the adjacent cells and ischaemic anoxia results in degeneration and necrosis. PAS staining cells. the deposition of amyloid is found between capillary and islet cells leading to islet cell destruction and development of Diabetes mellitus.In renal amyloidosis.

Out of many definitions offered. Histogenesis Benign Behaviour Malignant -carcinoma -sarcoma -oma I. mixed tumours (Involves more than one cell type arising from a single germinal layer) and compound tumours (Cells arising from all germinal layers). Simple tumours: Epithelial cells Mesenchymal cells Others -oma -oma -oma I I. I I I. S. ―A neoplasm is a new growth of cells which      Proliferate continuously without control Bearing a considerable resemblance to the healthy cells from which they arise Have no orderly structural arrangement Serve no useful function Have no clearly understood cause (Now a few causes of neoplasms have been identified)‖. The term cancer is used to indicate malignant tumours. Based on histogenesis. while malignant tumours originating from epithelial cells carry the suffix carcinoma and mesenchymal cells carry the suffix sarcoma. CLASSIFICATION OF NEOPLASM  Tumours are classified based on histogenesis (Cell of origin) and behavioral pattern (Dangerous to life or not). Mixed tumours Benign mixed tumour Malignant mixed tumour Immature teratoma Compound tumours Mature teratoma . Tumour the term meaning swelling is currently restricted to neoplasms. No. the following definition given by Mallory (1914) is satisfactory.Definitions The simple meaning of neoplasia is new growth. All benign tumours have the suffix –oma. Sastry (1986) added that neoplasm continues to grow even after the cessation of the stimuli which evoked the growth response. the neoplasms are classified as simple tumours (Involvement of one cell type). Nomenclature  The nomenclature of neoplasm has two components: an initial part (Prefix) that indicates the type of cell (Histogenesis) and the following part (Suffix) indicates the benign or malignant nature of neoplasm. Tumours are further classified based on behavioral pattern as benign (not ordinarily fatal) and malignant (usually fatal).

Epidermis ii.Histological classification of neoplasms Benign Epithelial i. Mucoid connective tissue iii. Hair follicle ii. Cartilage v. Bone Blood vessel Lymph vessel Smooth muscle Striated muscle Histiocyte Mast cell Fibroma Myxoma Lipoma Chondroma Osteoma Angioma or haemangioma Lymphangioma Leiomyoma Rhabdomyoma Histiocytoma Mastocytoma Fibrosarcoma Myxosarcoma Liposarcoma Chondrosarcoma Osteosarcoma Haemangiosarcoma Lymphangiosarcoma Leiomyosarcoma Rhabdomyosarcoma Trichoepithelioma Adenoma of respective gland Adenocarcinoma Adenocarcinoma Malignant Malignant histiocytoma or histiocytic sarcoma Malignant mast cell tumour or mast cell sarcoma Haemopoietic tissue i. Monocyte iv. Lymphocyte ii. Sebaceous/Sweat/Peria nal gland Non glandular epithelium Glandular surface Glandular epithelium Papilloma Polyp Adenoma Carcinoma Adenocarcinoma Adenocarcinoma Mesenchymal i. Fibrocyte ii. Basal cell (Skin adnexae) Papilloma Squamous cell carcinoma Basal cell carcinoma Adnexae i. Adipose connective tissue iv. Granulocyte Lymphocytoma - Lymphosarcoma Myeloma Monocytic leukemia Myelogenous leukemia or granulocytic leukemia . Plasma cell iii.

Islet cell Nephroblastoma Insulinoma (β cell adenoma) Malignant nephroblastoma Malignant insulinoma Melanoma Renal tubular adenoma Transitional cell papilloma Hydatidiform mole Seminoma Malignant melanoma Renal cell carcinoma Transitional cell carcinoma Choriocarcinoma Seminoma or Embryonal carcinoma . Bronchial epithelium - i. germ cells) vi. Oligodendroglia iii. aortic body) Pheochromocytoma Malignant pheochromocytoma Chemodectoma or Non chromaffin paraganglioma Malignant chemodectoma or Non chromaffin paragangliom Others i. Kidney vii. Synovial membrane ii. NeuroectodermMelanocyte ii. Myoloblast Mesothelium i. Meninges - Reticulum cell sarcoma Erythroid leukemia Myeloid leukemia Synovioma Meningioma Synovial carcinoma Meningioma or invasive meningioma Bronchogenic carcinoma Nervous tissue iii. Chromaffin paraganglia (adrenal medulla) vii. Schwann cells v. Astrocyte ii. Non chromaffin paraganglia (Carotid body. Nerve cell Astrocytoma Oligodendroglioma Ependymoma Schwannoma (neurilemmoma) Neuroblastoma or Ganglioneuroma Astrocytoma Oligodendroglioma Ependymoma Neurilemmoma Malignant neuroblastoma or Malignant ganglioneuroma vi. Erythroblasts vii. Reticulum cells vi.v. Spermatogonic epithelium (Testicular epithelium. Placental epithelium (Trophoblast) v. Renal epithelium iii. Urinary tract epithelium (Transitional) iv. Ependyma iv.

some are atypical Malignant Spontaneous regression Occurs Invasion Metastasis Basement membrane Blood vessel formation Degenerative and necrotic changes Recurrence Absent Absent Intact Moderate Absent as the blood supply is adequate Do not recur Destruction of adjacent Little tissues Cell structure Anaplasia Polarity Cellular pleomorphism Anisokaryosis Number of nucleus Nucleolus Nucleolar to nucleus ratio Cytoplasm to nuclear ratio Mitosis Typical to adult tissue Absent. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 19 20 21 22 Features Occurrence of nodule or mass Shape of nodule Encapsulation Rate of growth Growth Single Round. No. resembles cells from which they originate Maintained Absent Absent Not altered No change Not altered Not altered A few in number. prominent and multiple Increased Decreased Abundant.viii. elliptical or wart-like and pedunculated Present Slow Limited Benign Single or multiple Irregular Absent Rapid Unceasing Do not occur Present Present Broken Numerous Present because of inadequate blood supply Recurs after apparent removal Extensive Not typical to that of adult tissue Present Lost Present Present Multiple (Tumour giant cell) Enlarged. Liver ix. Sertoli cell Hepatoma Sertoli cell tumour Hepatocellular carcinoma Sertoli cell tumour DIFFERENCE BETWEEN BENIGN AND MALIGNANT TUMOURS S. Typical .

Epithelial neoplasms are common in old age. o Human e.23 Death Do not occur except if the tumour involves vital organs like heart. metast destruction CAUSES / ETIOLOGY OF NEOPLASMS Predisposing causes Definite causes      Hereditary Breed Age colour Hormones    Physical Chemical Biological Predispoing causes Hereditary   Hereditary predisposition is observed for some tumours. e. mammary and uterine cancer. sarcomas o Congenital e. lack of pigmentation may lead to occurrence of tumours.g. retinoblastoma and colon.g. o Lymphoid leucosis in poultry Age The period of life at which cancer appears is called cancer age. C3H. .Neuroblastoma. nephroblastoma Colour (Pigmentation)  Melanin pigment produced by melanocyte protects skin against UV rays of sun. Species Cancer age Dog Cattle Human  5 years 8-10 years 50 years Older age o This may be attributed to exposure to carcinogen and accumulation of somatic mutations. . prostate. ovarian. This is due to simple recessive Mendelian factor. However some tumour occurs at young age. The malignant tumours usually occur in old age.g. Certain strains of mice are highly susceptible to mammary and liver tumours.g. Hence. brain Usually occurs depending on the invasion. e.

Progesterone . methylcholanthracene (Chlorinated hydrocarbons).skin tumour I131 .ocular squamous cell carcinoma Hormones  Hormones like estrogen and progesterone may play a role to predispose animals to cancer. Xeroderma pigmentosum . X ray .Primary tumour Definite causes Physical         Solar radiation. Examples of major chemical carcinogens  Direct acting o Alkylating agents .a genetic disease of human in which enzymes required for DNA repair are lacking.malignant melanoma (especially old age).Dog .β propiolactone. hence exposure to UV ray of sunlight results in dry pigmented skin. UV radiation (UVB 280-320 nm) causes pyrimidine dimers injuring DNA causing mutation and tumours. light skinned animals and exposure of the area. β. e. Mammary tumour .g.e. eg. X rays and gamma radiation and particulate radiation (α. Yamagiwa and Itchikawa produced cancer in rabbit ears with repeated application of coal tar i. Estrogen .Mammary tumour in dogs ans cats. In 1915. Hereford cattle .osteosarcoma and leukaemia (painters of watches and clocks) Chemicals Sir Percival Pott (1775) was the first scientist to identify chemical agent to cause of cancer. Other potent chemical carcinogens are benzanthracene. ovarian carcinoma.Mammary tumour. Whole body radiation can cause leukaemia Radiation includes elctromagnetic radiation (UV rays. experimental carcinogenesis. Kenneway and Cook purified the carcinogen 3.cutaneous tumours It is associated with areas where sunlight is intense. Dimethylsulfoxide .benzapyrene from crude tar.thyroid adenoma Radium . proton and neutrons) which are carcinogens. Grey and white horses . 4 .

1 2 Initiator Promoter Tumour produced Aflatoxin B1 Methyl sterculate Hepatocellular carcinoma in trout Benzapyrene Croton oil Squamous cell carcinoma inn mouse skin Biological causes   Bacteria: Helicobacter pylori – gastric cancer and lymphoma in man. aldrin.It requires metabolic conversion to become ultimate carcinogen to induce cancer.benzanthracene o Nitrosoamines and nitrosoamides . dieldrin Mechanism of chemical carcinogenesis Initiation promotion model S.1 acetyl imidasone Indirect acting or procarcinogen .Oesophageal fibrosarcoma and osteosarcoma in dogs o Cysticercus fasciolaris – fibrosarcoma in rat liver .vinyl chloride. Helicobacter hepaticus – hepatocellular carcinoma in mice Parasites o Spirocera lupi .No. o Polycyclic and heterocyclic hydrocarbons . o Aceylating agents .

myxoma in rabbit  Herpes virus – Marek‘s disease chicken o Oncogenic RNA viruses  Retroviruses – Lymphoid leucosis  Rous sarcoma virus – Tumours in poultry o o Ellerman and Bang (1908) were the first to demonstrate viral carcinogenesis and later by Rous. neoplastic cell motility (amoeboid movement of fibroblast due to lack of contact inhibition and cohesiveness) and accumulation of metabolites (e. Eimeria stiedae – bile duct tumour in rabbits Schistosoma haematobium – bladder cancer in man Viruses o DNA viruses – Papova. Lactic acid) and enzymes like hyaluronidase which hydrolyse cementing substance. Peyton Rous (1910) produced similar results with fowl sarcomas. Invasion is defined as movement of neoplasm directly through tissue planes. Invasion of neoplasm into an adjacent tissue is facilitated by breaking of basement membrane by proteolysis (collagenases ) and migration through interstitial tissue through the help of proteolytic enzymes or proteases. Increased negative charges on plasma membranes. . human papilloma  Pox viruses – fibroma. Infiltration of neighbouring tissues: The malignant tumour infiltrates and invades the adjacent tissues because of rapid multiplication of cells. Gross (1953) induced leukaemia with cell free filtrate in mice. SPREAD OF NEOPLASM The neoplasm spreads by   Invasion Metastasis These are hall marks of malignant tumour. bovine papilloma. Metastasis can occur by    Implantation Haematogenous spread Lymphatic spread The invasion and metastasis are characteristic features of malignant neoplasm. Metastasis is defined as spread of neoplasm from primary to a distant site. Shope papilloma. Implantation is establishment of neoplasm on new surfaces especially body cavities. canine oral papilloma. decreased calcium ion content and lack of cohesiveness facilitate the process of invasion. Infiltration  Infiltration into tissue spaces o Invasion depends upon the type of tissue. Soft and loose tissue can be infiltrated easily while it is difficult to infiltrate hard tissues.g.

Permeation can also occur wherein the tumour cells extend along lymphatics by growing along endothelium. transcoelomic spread or soil theory or seeding into pericardial. Inoculation . e. Penetrate muscle fibres Lymphatic spread  This occurs by emboli formed by clumping of neoplastic cells.rare hazard in surgery where tumour cell can be implanted in edges of the wound and new tumour develops. Tumour emboli involving portal vein induces tumour in the liver and those spread through systemic vein produce metastases in lungs. Cancer of ovary and stomach Implantation    By natural passages . Carcinomas spread by lymphatics.Lymph node metastasis Mammary Tumour . the tumour cell casts get and implanted. Intracellular infiltration o Tumour cells can also traverse cell. peritoneal and subarachnoid membranes.Dog Metastasis . Coitus . Blood spread  Neoplastic cells frequently invade veins and capillaries.venereal tumour of dogs gets transmitted by this way. Spread by nerves  This occurs by permeation through perineural lymphatics with degeneration of nerves. Mammary tumor . Neoplastic cells reach regional lymph nodes and are trapped in the cortical sinuses and following proliferation of cells lead to secondary tumours.g.In hollow organs.Dog . Transcoelomic spread (Spread in body cavities)  In implantation.g. e. the lack of cohesiveness of neoplastic cells favours implantation into the surrounding body cavities i. pleural.secondary tumour .e. e.g.Lung Mechanism of invasion and spread . Tumour of renal pelvis get washed down in bladder and implanted to form tumours.

Lung cancer spreads to adrenals and do not affect skeletal muscle. Invasion of extracellular matrix by tumour cell is an active process involving     Detachment of tumour cells from each other Attachment of tumour cells to matrix Degeneration of extracellular matrix Migration of tumour cells Detachment of tumour cells from each other which occur due to loosening of tumour cells which lack adhesion molecules. diversification. growth. Invasion of extracellular matrix 2. glycoproteins and proteoglycans. 1. This phenomenon is called homing of tumours.g. Normal epithelial cells have receptors for basement membrane laminin on basal surface while carcinoma cells have many more receptors. e. Degeneration of extracellular matrix occurs due to proteolytic enzymes elaborated by tumour cells. etc. angiogenesis ↓ Metastatic subclone ↓ Adhesion to and invasion of basement membrane .g. Migration of tumour cells: The locomotion of tumour cell is by amoeboid movement by throwing pseudopodia through the degraded basement membrane. Spread of tumours Clonal expansion. Site of metastasis depends on location of primary tumour and its vascular and lymphatic drainage and organ tropism depends on cellular attraction. Vascular dissemination and homing of cells  Once in the circulation those tumour cells which survive host immunity by binding with circulating lymphocytes and platelets adhere to vascular endothelium and exits through basement membrane. Vascular dissemination and homing of cells Invasion of extracellular matrix Extracellular matrix is divided into two types   Basement membrane Interstitial connective tissue Extracellular matrix is composed of collagen. Attachment of tumour cells to matrix by proteins like laminin and fibronectin through the receptors.The spread of tumour is divided into two phases. e. E-cadherin.

The immune surveillance mechanism recognises and destroys non-self tumour cells. .↓ Passage through extracellular matrix ↓ Intravasation ↓ Interaction with host lymphoid cells ↓ Tumour cell embolus ↓ Adhesion to the endothelium ↓ Breaking the basement membrane ↓ Extravasation ↓ Metastatic deposit ↓ Angiogenesis ↓ Growth TUMOUR IMMUNITY  The genetic alteration that occurs during malignant transformation may result in expression of proteins that are regarded as non-self of foreign by the immune system.

e. Differentiation antigens are peculiar to different stage in which cancer cells are arrested and useful differentiator marker in diagnosis of cancer. They are of two types 1. Two types of tumour associated antigen (TAA) 1. Natural killers cells (NK cells) o These cells can destroy tumour cells without prior sensitization thereby provides first line of defence against tumour cells. present on tumour and also some normal cells Tumour specific antigens are found in chemically induced tumour of rodents which express unique antigen not shared by other histologically identical tumour induced by the same chemical even in the same animal. present only on tumour cells and not on any other cells 2. e.Embryonic antigens which are normally expressed in developing embryos.     Cytotoxic T lymphocytes (CD8+ T cells) o Cytotoxic T lymphocytes are important in chemically induced tumours. Tumour specific antigen (TSA). a cytokine secreted by T cells and NK cells. It plays a protective role in virus associated neoplasms. Tumour associated antigen are not specific to individual tumour and shared by similar tumour in other animal. Carcinoembryonic antigen (CEA) 2. Macrophages o Activated macrophages show selective cytotoxicity against tumour cells. Alpha fetoprotein. The cells destroy the tumour cells by recognising MHC class I antigen expressed on tumour cells. These cells kill the tumour cells through reactive oxygen species or secretion of tumour necrosis factor (TNF). Tumour specific antigen is an altered form of normal protein occurring due to mutation of gene.g.Tumour antigens   The tumour cells may differ antigenically from normal cells and can either gain or lose cell membrane molecules. is a potent activator of macrophage. T cells. Tumour associated antigen (TAA). These are recognised by CD8+ cytotoxic T lymphocytes.g. After activation with interleukin 2. Oncofetal antigen . Antibody dependant cellular cytotoxicity (ADCC) . Anti-tumour effector mechanism Both cell mediated immunity and hormonal immunity (activation of complement. γ interferon. Prostatic and lymphoid tumour in man Since tumour associated antigens are normal self protein they do not evoke immune response but of value in diagnosis of certain and immune therapy. NK cells and macrophages may work together in anti-tumour activity. Each mutated protein combines with MHC class I protein to become an antigen. ADCC) have antitumour activities. natural killer cells can destroy a wide range of animal and human tumours.

o Ectopic hormone production or syndrome . location and tissue of origin and secondarily due to spread to other organs. CD95 L) Inactivation or mutation of tumour suppressor and apototic genes. The TNFα plays a role on suppressing the appetite and inhibition of action of lipoprotein. p53. e.It is due to loss of body fat and wasting besides profound weakness.g. ADCC may be mediated by neutrophils. potent immunosuppressor Evasion of immune system (Immunosurveillance) This may occur through different mechanisms. Infection . Paraneoplastic syndrome the symptoms that are not directly related to spread of tumour or elaboration of hormones indigenous to the tissue from which tumours arise.Masculinisation Anaemia may be due to decreased bone marrow response. Immunosuppression  Many oncogenic substances suppress host immune response (chemicals. Malignant ascites. This will lead to excessive protein degradation and negative nitrogen balance. Hormonal effects o Parathyroid tumour – Osteoporosis and big head in horses o Tumour of sertoli cells – Feminization o Hypoglycaemia . o Obstruction Effect  Ureter Hydronephrosis  Bronchus Collapse of lung  Intestine Intussusception Tissue of origin . eosinophils. Cancer cachexia .            Pressure atrophy . Location . macrophages and NK cells.2 EFFECTS OF NEOPLASIA The effects of neoplasia primarily may be due to the size. it causes death.o It is involving killing those cells that bear receptor for Fc portion of IgG. TGF β.If the tumour involves vital organs like heart and brain. ionising radiation) and tumours or tumour products e.Insulinoma o Arrhenoblastoma in female . Target cell coated by antibody are destroyed without phagocytosis or complement fixation.The tumour may cause obstruction of luminal organs by narrowing luminal space interfering with functional activity.The expanding tumour may cause pressure atrophy of some organs especially through pressure on blood and lymphatic vessels thereby interfering with nutrition and fluid exchanges to tissues.Surface tumours may be ulcerated and subsequently infected. haemorrhages and haemolysis Thrombocytopenia may also occur. Exudate in serous cavities – Tumour cells deposited on serous membranes incites an inflammatory response with exudation.g. Monoclonal gammopathies occur in plasma cell tumours. Eg. BCL .        Non expression of new antigens that are immunogenic Failure to express host immune stimulatory molecules required for activation of T-cells Lack or poor expression of MHC antigen by tumour cells Overwhelming the immune system and rapid proliferation of malignant cells or too small tumour cells in initial stage to evoke immune response Secretion of immunosuppression molecules Expression of death inducing ligands (Fas L.

Chemical and serological tests o No such reliable tests are available in veterinary practice. Lung cancer . Flow cytometry o This can identify cell population. mitosis. However. Lymphoma in dogs and cats.  e. This may be cell surface proteins.g. cytoplasmic proteins. e. this is much applicable in small animals and of limited use in veterinary practice. Biopsy (histopathology) o Reliable method by which diagnosis can be made based on cellular characteristics (microscopically . loss of polarity) which indicate malignancy (Also see staging and grading) Radiology o Radiological examination of viscera and bone may show primary or secondary lesions. These cells can be collected and suitably stained for making a diagnosis. southern and western blot analysis can be used. This test is known as papa test.g. This technique is used in human medicine for early diagnosis of cervical. immunophenotyping of lymphocytes Immunohistochemistry method o Immunohistochemistry can be used to identify the type of cell (epithelial cellcytokeratin marker) and malignancy of tumours. cystic. Cells can be collected most commonly through fine needle aspiration biopsy. Molecular methods o Polymerase chain reaction (PCR) will be helpful in differentiating monoclonal tumours. The production of hormones by the neoplastic cells which are not of endocrine origin. . scraping and brushing. uterine and bronchogenic tumours. Pappanicolaou is considered as father of cytology. o DNA probe analysis. Cytology o It is examination of cells which can be applied in diagnosing cancer. Tumour markers  This is biochemical indicator to identify the presence of tumours.          Clinical diagnosis o Based on the gross features (Papilloma. e. Cellular characteristics for malignancy have to be seen. o Acridine orange staining . However.The cytoplasm of malignant cells will show brick red fluorescence and nucleus will show apple green fluorescence. fibrotic. nodular tumour) o Any nonhealing growth or lesion and growth of profusely bleeding nature are to be suspected for possible cancer. metastasis.  DIAGNOSIS OF CANCER Early diagnosis of cancer will help in treatment by therapy or surgical intervention. northern. invasion.insulin production Hypercalcaemia occurs when neoplastic cell synthesises and secretion of peptides that mimick parathyroid hormones or tumour affecting producing humoral factors and stimulating osteoclasts.g. enzymes and hormones. in human medicine chemical/enzyme tests are available to diagnose prostatic cancer and bone cancer. Exfoliative cytology o Neoplastic cells show loss of cohesiveness and those arising on the surface are easily detached and exfoliated. Other methods are impression. This can be stained by Romanowsky‘s stains and haematoxylin and eosin stain.anaplasia.ACTH production  Fibrosarcoma .

tumours can be classified as grade I. III. Primary tumour   T0 – no evidence of tumour T1 – tumour confined to primary site . IV (grade I for the least and grade IV for the most anaplastic) Clinical staging of cancer (TNM classification) This is based on    Size of the primary tumour -T Extent of spread to regional lymph node -N Presence or absence of metastasis -M Clinical staging should be combined with histological analysis such as grading of tumours which is helpful in prediction of survival of cancer patients. metastasis and number of mitoses. II.Uses    To confirm diagnosis To determine response to therapy To indicate relapse after treatment Markers Associated tumours Oncofetal proteins Alpha fetoprotein Hepatocellular carcinoma Germ cell tumour of testes Carcinoembryonic antigen Carcinoma of colon. invasion. pancreas and stomach Hormones Calcitonin Catecholamines Thyroid medullary carcinoma Pheochromocytoma Isoenzymes Prostatic acid isophosphatase Prostatic tumour (human) Specific protein Immunoglobulins Multiple myeloma Mucin CA 125 Ovarian tumour GRADING AND STAGING OF CANCERS Based on the extent of malignant features like cellular characters (differentiation and anaplasia).

 T2 – tumour invades adjacent tissues Lymph nodes    N0 – no evidence of tumour N1 – regional lymph node involvement N2 – distant lymph node involvement Metastases    M0 – no evidence of tumour M1 – tumour in same organ or cavity as primary M2 – distant metastases .